Classic models for dynamic contrast‐enhanced MRI
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Dynamic contrast‐enhanced MRI (DCE‐MRI) is a functional MRI method where T1 ‐weighted MR images are acquired dynamically after bolus injection of a contrast agent. The data can be interpreted in terms of physiological tissue characteristics by applying the principles of tracer‐kinetic modelling. In the brain, DCE‐MRI enables measurement of cerebral blood flow (CBF), cerebral blood volume (CBV), blood–brain barrier (BBB) permeability–surface area product (PS) and the volume of the interstitium (ve). These parameters can be combined to form others such as the volume‐transfer constant Ktrans, the extraction fraction E and the contrast‐agent mean transit times through the intra‐ and extravascular spaces. A first generation of tracer‐kinetic models for DCE‐MRI was develo...
DTI of human skeletal muscle: the effects of diffusion encoding parameters, signal‐to‐noise ratio and T2 on tensor indices and fiber tracts
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In this study, we have performed simulations to address the effects of diffusion encoding parameters, signal‐to‐noise ratio (SNR) and T2 on skeletal muscle diffusion tensor indices and fiber tracts. Where appropriate, simulations were corroborated and validated by in vivo diffusion tensor imaging (DTI) of human skeletal muscle. Specifically, we have addressed: (i) the accuracy and precision of the diffusion parameters and eigenvectors at different SNR levels; (ii) the effects of the diffusion gradient direction encoding scheme; (iii) the optimal b value for diffusion tensor estimation; (iv) the effects of changes in skeletal muscle T2; and, finally, the influence of SNR on fiber tractography and derived (v) fiber lengths, (vi) pennation angles and (vii) fiber curvatures. We conclude th...
Measuring anisotropic muscle stiffness properties using elastography
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This study used the noninvasive MR elastography (MRE) technique, in combination with diffusion tensor imaging (DTI), to measure shear modulus anisotropy in the human skeletal muscle in the lower leg. Shear modulus measurements parallel and perpendicular to the fibre direction were made in 10 healthy subjects in the medial gastrocnemius, soleus and tibialis anterior muscles. The results showed significant differences in the medial gastrocnemius (μ‖ =0.86 ± 0.15 kPa; μ⊥ = 0.66 ± 0.19 kPa, P < 0.001), soleus (μ‖ = 0.83 ± 0.22 kPa; μ⊥ = 0.65 ± 0.13 kPa, P < 0.001) and the tibialis anterior (μ‖ = 0.78 ± 0.24 kPa; μ⊥ = 0.66 ± 0.16 kPa, P = 0.03) muscles, where the shear modulus measured in the direction paralle...
Ratiometric analysis in hyperpolarized NMR (I): test of the two‐site exchange model and the quantification of reaction rate constants
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In this study, we developed a framework to test the validity of the assumption of stable reaction rate constants and the two‐site exchange model in vivo via ratiometric fitting of the time courses of the signal ratio L(t)/P(t). Our analysis provided evidence that the LDH enzymatic kinetics observed by hyperpolarized NMR are in near‐equilibrium and satisfy the two‐site exchange model for only a specific time window. In addition, we quantified both the forward and reverse exchange rate constants of the LDH reaction for the transgenic and mouse xenograft models of breast cancer using the ratio fitting method developed, which includes only two modeling parameters and is less sensitive to the influence of instrument settings/protocols, such as flip angles, degree of polarization and trace...
Feasibility of measuring prostate perfusion with arterial spin labeling
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(Source: NMR in Biomedicine)
MRI of tissues with short T2s and T2*s. Wiley ISBN 978‐0‐470‐68835‐9
G. M.
Bydder,
G. D.
Fullerton and
I. R.
Young
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(Source: NMR in Biomedicine)
Accelerating hyperpolarized metabolic imaging of the heart by exploiting spatiotemporal correlations
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Hyperpolarized 13C‐labeled pyruvate is a promising tool to investigate cardiac metabolism. It has been shown that changes in substrate metabolism occur following the induction of ischemia. To investigate the metabolic changes that are confined to spatial regions, high spatiotemporal resolution is required. The present work exploits both spatial and temporal correlations using k–t principal component analysis (PCA) to undersample the spatiotemporal domain, thereby speeding up data acquisition. A numerical model was implemented to investigate optimal acquisition and reconstruction parameters for pyruvate, lactate and bicarbonate maps of the heart. Subsequently, prospectively undersampled in vivo data on rat hearts were acquired using a combination of spectral–spatial signal excitation ...
In vivo MRI cell tracking using perfluorocarbon probes and fluorine‐19 detection
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This article presents a brief review of preclinical in vivo cell‐tracking methods and applications using perfluorocarbon (PFC) probes and fluorine‐19 (19F) MRI detection. Detection of the 19F signal offers high cell specificity and quantification ability in spin density‐weighted MR images. We discuss the compositions of matter, methods and applications of PFC‐based cell tracking using ex vivo and in situ PFC labeling in preclinical studies of inflammation and cellular therapeutics. We also address the potential applicability of 19F cell tracking to clinical trials. Copyright © 2013 John Wiley & Sons, Ltd. This review article focuses on in vivo cell tracking methods and applications using perfluorocarbon (PFC) probes and fluorine‐19 (19F) MRI detection. Detection of the 19F s...
Issue Information
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No abstract is available for this article. (Source: NMR in Biomedicine)
MRI confirms loss of blood–brain barrier integrity in a mouse model of disseminated candidiasis
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This article is a U.S. Government work and is in the public domain in the USA. MRI of mice infected with Candida albicans using gadolinium‐enhanced vascular contrast (A) demonstrates that the integrity of the blood–brain barrier is lost on infection. Dynamic contrast studies for cortical and hippocampal regions (B) show first‐pass recovery indicating an intact barrier in uninfected mice and vascular leakage in infected brains. Two‐photon microscopy through a surgically thinned skull window (C) shows filamentous and yeast forms of C. albicans (green) colonizing the meninges and brain parenchyma, 3 days following intravenous inoculation. (Source: NMR in Biomedicine)
Nuclear spin singlet states as a contrast mechanism for NMR spectroscopy
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Nuclear magnetic resonance (NMR) spectra of complex chemical mixtures often contain unresolved or hidden spectral components, especially when strong background signals overlap weaker peaks. In this article we demonstrate a quantum filter utilizing nuclear spin singlet states, which allows undesired NMR spectral background to be removed and target spectral peaks to be uncovered. The quantum filter is implemented by creating a nuclear spin singlet state with spin quantum numbers j = 0, mz = 0 in a target molecule, applying a continuous RF field to both preserve the singlet state and saturate the magnetization of undesired molecules and then mapping the target molecule singlet state back into an NMR observable state so that its spectrum can be read out unambiguously. The preparation...
Quantitative mouse renal perfusion using arterial spin labeling
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Information on renal perfusion is essential for the diagnosis and prognosis of kidney function. Quantification using gadolinium chelates is limited as a result of filtration through renal glomeruli and safety concerns in patients with kidney dysfunction. Arterial spin labeling MRI is a noninvasive technique for perfusion quantification that has been applied to humans and animals. However, because of the low sensitivity and vulnerability to motion and susceptibility artifacts, its application to mice has been challenging. In this article, mouse renal perfusion was studied using flow‐sensitive alternating inversion recovery at 7 T. Good perfusion image quality was obtained with spin‐echo echo‐planar imaging after controlling for respiratory, susceptibility and fat artifacts by trigge...
A comparative study of short‐ and long‐TE 1H MRS at 3 T for in vivo detection of 2‐hydroxyglutarate in brain tumors
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We report a comparative study of the utility of short‐ and long‐TE point‐resolved spectroscopy (PRESS) for the detection of the oncometabolite 2‐hydroxyglutarate (2HG) at 3 T. The performance of the methods is evaluated using data from phantoms, seven healthy volunteers and 22 subjects with isocitrate dehydrogenase (IDH)‐mutated gliomas. The results indicate that TE = 97 ms provides a higher selectivity of 2HG signals than at short TEs, and that this improved capability is gained when appropriate basis spectra are used for spectral fitting. (Source: NMR in Biomedicine)
Assessment of gadoxetate DCE‐MRI as a biomarker of hepatobiliary transporter inhibition
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Drug‐induced liver injury (DILI) is a clinically important adverse drug reaction, which prevents the development of many otherwise safe and effective new drugs. Currently, there is a lack of sensitive and specific biomarkers that can be used to predict, assess and manage this toxicity. The aim of this work was to evaluate gadoxetate‐enhanced MRI as a potential novel biomarker of hepatobiliary transporter inhibition in the rat. Initially, the volume fraction of extracellular space in the liver was determined using gadopentetate to enable an estimation of the gadoxetate concentration in hepatocytes. Using this information, a compartmental model was developed to characterise the pharmacokinetics of hepatic uptake and biliary excretion of gadoxetate. Subsequently, we explored the impact of...
Fiber type characterization in skeletal muscle by diffusion tensor imaging
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Fiber type distribution within a skeletal muscle, i.e. the quantification of the relative amount of type 1 (slow‐twitching) and type 2 (fast‐twitching) muscle fibers, is of great interest for the monitoring of the effects of training or the treatment of muscle diseases. The purpose of this study was to determine the feasibility of diffusion tensor imaging (DTI) as a tool for noninvasive fiber type quantification in human skeletal muscle. The right calves of 12 healthy volunteers were examined using DTI at 1.5 T. Standard DTI parameters, including fractional anisotropy (FA), and mean, radial and parallel diffusivity (MD, RD and PD, respectively), were determined in the soleus muscle. Fiber type proportion and mean fiber diameter within the soleus muscle were quantified from tissue spe...
Amide proton transfer imaging of the human breast at 7T: development and reproducibility
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Chemical exchange saturation transfer (CEST) can offer information about protons associated with mobile proteins through the amide proton transfer (APT) effect, which has been shown to discriminate tumor from healthy tissue and, more recently, has been suggested as a prognosticator of response to therapy. Despite this promise, APT effects are small (only a few percent of the total signal), and APT imaging is often prone to artifacts resulting from system instability. Here we present a procedure that enables the detection of APT effects in the human breast at 7T while mitigating these issues. Adequate signal‐to‐noise ratio (SNR) was achieved via an optimized quadrature RF breast coil and 3D acquisitions. To reduce the influence of fat, effective fat suppression schemes were developed th...
Mapping glutamate in subcortical brain structures using high‐resolution GluCEST MRI
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In vivo measurement of glutamate (Glu) in brain subcortex can elucidate the role these structures play in cognition and neuropsychiatric disorders. However, accurate quantification of Glu in subcortical regions is challenging. Recently, a novel MRI method based on the Glu chemical exchange saturation transfer (GluCEST) effect has been developed for detecting brain Glu in millimolar concentrations. Here, we use GluCEST to map Glu distributions in subcortical structures of the human brain (e.g. amygdala, hippocampus). Overall, GluCEST was ~40% higher in gray matter than in white matter. Within the subcortical gray matters, amygdala showed the highest GluCEST contrast. Utilizing MR spectroscopic data, in vivo GluCEST detection sensitivity (~0.8% mM−1) in subcortical gray matter was evaluate...
A calibration‐based approach to real‐time in vivo monitoring of pyruvate C1 and C2 polarization using the JCC spectral asymmetry
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A calibration‐based technique for real‐time measurement of pyruvate polarization by partial integral analysis of the doublet from the neighbouring J‐coupled carbon is presented. In vitro calibration data relating the C2 and C1 asymmetries to the instantaneous C1 and C2 polarizations, respectively, were acquired in blood. The feasibility of using the in vitro calibration data to determine the instantaneous in vivo C1 and C2 polarizations was demonstrated in the analysis of rat kidney and pig heart spectral data. An approach for incorporating this technique into in vivo protocols is proposed. Copyright © 2013 John Wiley & Sons, Ltd. Calibration data relating spectral asymmetry and polarization in blood were used to monitor the instantaneous C1 and C2 polarizations of [1,2‐13C2] ...
Adiabatic multi‐echo 31P spectroscopic imaging (AMESING) at 7 T for the measurement of transverse relaxation times and regaining of sensitivity in tissues with short T2* values
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An adiabatic multi‐echo spectroscopic imaging (AMESING) sequence, used for 31P MRSI, with spherical k‐space sampling and compensated phase‐encoding gradients, was implemented on a whole‐body 7‐T MR system. One free induction decay (FID) and up to five symmetric echoes can be acquired with this sequence. In tissues with low T2* and high T2, this can theoretically lead to a potential maximum signal‐to‐noise ratio (SNR) increase of almost a factor of three, compared with a conventional FID acquisition with Ernst‐angle excitation. However, with T2 values being, in practice, ≤400 ms, a maximum enhancement of approximately two compared with low flip Ernst‐angle excitation should be feasible. The multi‐echo sequence enables the determination of localized T2 values, and was...
Measuring mitochondrial metabolism in rat brain in vivo using MR Spectroscopy of hyperpolarized [2‐13C]pyruvate
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This study demonstrates, for the first time, that hyperpolarized [2‐13C]Pyr can be used for the in vivo investigation of mitochondrial function and tricarboxylic acid cycle metabolism in brain. Copyright © 2013 John Wiley & Sons, Ltd. Single‐time‐point chemical shift imaging data were acquired from rat brain in vivo after the administration of 2–3.5 mL of 125 mm hyperpolarized [2‐13C]pyruvate, using a custom‐built 13C surface coil. The downstream metabolic products [5‐13C]glutamate and [1‐13C]citrate were detected in the brain, and 13C‐labeled acetylcarnitine was observed primarily from the surrounding muscle/fat tissues. The fate of acetyl‐coenzyme A (acetyl‐CoA) in the brain was further investigated by infusing dichloroacetate (DCA), which upregulates pyruv...
Rapid multi‐echo measurement of brain metabolite T2 values at 7 T using a single‐shot spectroscopic Carr–Purcell–Meiboom–Gill sequence and prior information
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We present a method for the robust and accurate estimation of brain metabolite transverse relaxation times (T2) from multiple spin‐echo data acquired with a single‐shot Carr–Purcell–Meiboom–Gill (CPMG) spectroscopic sequence. Each acquired echo consists of a small number of complex time‐domain data points. The amplitudes of the spectral components in each echo are calculated by solving a set of linear equations in which previously estimated frequencies and linewidths serve as prior information. These priors are obtained from a short MRS experiment in which a large number of time‐domain data points are acquired, and are subsequently estimated using linear prediction with singular value decomposition (LPSVD) processing. We show that this process can be used to accurately and ra...
Investigation of field and diffusion time dependence of the diffusion‐weighted signal at ultrahigh magnetic fields
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This study suggests that the observed differences in diffusion tensor imaging parameters between the two magnetic field strengths at short diffusion time may be related to differences in the apparent T2 values between the pools. Copyright © 2013 John Wiley & Sons, Ltd. In this work, we investigated the influence of high magnetic field strength (9.4 T and 14.1 T) and diffusion time on the diffusion‐weighted (DW) signal in the rat brain white matter. The diffusion tensor imaging (DTI)‐derived parameters of the restricted compartment displayed a differential sensitivity to B0 attributable to its apparent transverse relaxation time T2. The shortening of the pseudo‐T2 from the restricted compartment (DW) with B0 is likely to be more pronounced than the apparent T2 changes in the ...
High‐resolution magic angle spinning 1H MRS in prostate cancer
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Prostate cancer (PCa) is the most frequently diagnosed malignancy in men worldwide, largely as a result of the increased use of the annual serum prostate‐specific antigen (PSA) screening test for detection. PSA screening has saved lives, but it has also resulted in the overtreatment of many patients with PCa because of a limited ability to accurately localize and characterize PCa lesions through imaging. High‐resolution magic angle spinning (HRMAS) 1H MRS has proven to be a strong potential clinical tool for PCa diagnosis and prognosis. The HRMAS technique allows valuable metabolic information to be obtained from ex vivo intact tissue samples and also enables the performance of histopathology on the same tissue specimens. Studies have found that the quantification of individual metabol...
Manganese‐enhanced MRI of rat brain based on slow cerebral delivery of manganese(II) with silica‐encapsulated MnxFe1–xO nanoparticles
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In this work, we report a monodisperse bifunctional nanoparticle system, MIO@SiO2‐RITC, as an MRI contrast agent [core, manganese iron oxide (MIO); shell, amorphous silica conjugated with rhodamine B isothiocyanate (RITC)]. It was prepared by thermal decomposition and modified microemulsion methods. The nanoparticles with varying iron to manganese ratios displayed different saturated magnetizations and relaxivities. In vivo MRI of rats injected intravenously with MIO@SiO2‐RITC nanoparticles exhibited enhancement of the T1 contrast in brain tissue, in particular a time‐delayed enhancement in the hippocampus, pituitary gland, striatum and cerebellum. This is attributable to the gradual degradation of MIO@SiO2‐RITC nanoparticles in the liver, resulting in the slow release of manganese...
A low‐cost, mechanically simple apparatus for measuring eddy current‐induced magnetic fields in MRI
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In this study, an apparatus is presented that accomplishes these tasks with a low‐cost, mechanically simple solution. The coil system consists of six transmit/receive RF coils immersed in a high‐molarity saline solution. The sensitivity and SNR following an excitation pulse are sufficiently high to allow accurate phase measurements during free‐induction decays; the intrinsic susceptibility matching of the materials, because of the unique design of the coil system, results in sufficiently narrow spectral line widths (mean of 19 Hz), and adjacent RF coils are highly decoupled (mean S12 of −47 dB). The temporal and spatial distributions of eddy currents following a gradient pulse are measured to validate the efficacy of the design, and the resultant amplitudes and time constants r...
In vitro mapping of 1H ultrashort T2* and T2 of porcine menisci
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In this study, mapping of ultrashort T2 and T2* of acutely isolated porcine menisci at B0 = 9.4 T was investigated. Maps of T2 were measured from a slice through the pars intermedia with a spin echo‐prepared two‐dimensional ultrashort‐TE T2 mapping technique published previously. T2* mapping was performed by two‐dimensional ultrashort‐TE MRI with variable acquisition delay. The measured signal decays were fitted by monoexponential, biexponential and Gaussian‐exponential fitting functions. The occurrence of Gaussian‐like signal decays is outlined theoretically. The quality of the curve fits was visualized by mapping the value δ = abs(1 – χ2red). For T2* mapping, the Gaussian‐exponential fit showed the best performance, whereas the monoexponential and biexponential ...
Improved efficiency on editing MRS of lactate and γ‐aminobutyric acid by inclusion of frequency offset corrected inversion pulses at high fields
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In this study, a Mescher–Garwood semi‐localization by adiabatic selection and refocusing (MEGA‐sLASER) editing sequence with refocusing FOCI pulses is presented for the measurement of GABA and lactate in the human brain. Metabolite detection efficiencies were improved by 20% and 75% for GABA and lactate, respectively, when compared with editing techniques that employ adiabatic radiofrequency refocusing pulses. The highly efficient MEGA‐sLASER sequence with refocusing FOCI pulses is an ideal and robust MRS editing technique for the measurement of weakly coupled metabolites at high field strengths. Copyright © 2013 John Wiley & Sons, Ltd. The detection efficiency in MRS editing techniques is limited by the chemical shift displacement artifact at high fields, particularly for spi...
31P NMR relaxation of cortical bone mineral at multiple magnetic field strengths and levels of demineralization
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Recent work has shown that solid‐state 1H and 31P MRI can provide detailed insight into bone matrix and mineral properties, thereby potentially enabling differentiation of osteoporosis from osteomalacia. However, 31P MRI of bone mineral is hampered by unfavorable relaxation properties. Hence, accurate knowledge of these properties is critical to optimizing MRI of bone phosphorus. In this work, 31P MRI signal‐to‐noise ratio (SNR) was predicted on the basis of T1 and T2* (effective transverse relaxation time) measured in lamb bone at six field strengths (1.5–11.7 T) and subsequently verified by 3D ultra‐short echo‐time and zero echo‐time imaging. Further, T1 was measured in deuterium‐exchanged bone and partially demineralized bone. 31P T2* was found to decrease from 220.3 ± ...
Role of MRI in prostate cancer detection
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The standard approach for the detection of prostate cancer ‐‐ prostate‐specific antigen (PSA) screening followed by transrectal ultrasonography (TRUS)‐guided biopsy ‐‐ has low sensitivity and provides limited information about the true extent and aggressiveness of the cancer. Improved methods are needed to assess the extent and aggressiveness of the cancer and to identify patients who will benefit from therapy. In recent years, there has been tremendous development of acquisition and processing tools for physiological and metabolic MRI techniques which play a potential role in the detection, localization and characterization of prostate cancer, such as dynamic contrast‐enhanced MRI (DCE‐MRI), diffusion‐weighted MRI (DW‐MRI) and/or proton MR spectroscopic imaging (1H MRS...
Issue Information
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No abstract is available for this article. (Source: NMR in Biomedicine)
Comparison of different MRI sequences in lesion detection and early response evaluation of diffuse large B‐cell lymphoma – a whole‐body MRI and diffusion‐weighted imaging study
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In conclusion, this study indicates that T2‐weighted imaging with fat suppression is the best conventional sequence for the detection of lesions and evaluation of the efficacy of chemotherapy in DLBCL. DWI with ADC mapping is an imaging modality with both diagnostic and prognostic value that could complement conventional MRI. Copyright © 2013 John Wiley & Sons, Ltd. Eighteen patients with diffuse large B‐cell lymphoma (DLBCL) were imaged by MRI prior to and 1 week after chemotherapy. The mean pre‐therapy apparent diffusion coefficient (ADC) was 0.68 × 10–3 mm2/s; it increased by 89% after treatment (p < 0.001), accompanied by a 65% decrease in tumor size. T2‐weighted imaging with fat suppression is the best conventional sequence for the detection of lesions a...
Perfusion deficits in patients with mild traumatic brain injury characterized by dynamic susceptibility contrast MRI
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In conclusion, rCBF calculated using AIFs selected from an automated approach demonstrated a good agreement with the corresponding results using manually selected AIFs. Group analysis of patients with mild TBI from a military population demonstrated scattered perfusion deficits, which showed significant correlations with measures of verbal memory, speed of reaction time and self‐report of stress symptoms. Published 2013. This article is a U.S. Government work and is in the public domain in the USA. Perfusion deficits in patients with mild traumatic brain injury from a military population were characterized by dynamic susceptibility contrast (DSC) imaging. Relative cerebral blood flow (rCBF) calculated using arterial input functions (AIFs) selected from an automated approach demonstrated ...
White matter integrity affected by depressive symptoms in migraine without aura: a tract‐based spatial statistics study
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Previous studies have proven that migraine and depression are bidirectionally linked. However, few studies have investigated white matter (WM) integrity affected by depressive symptoms in patients suffering from migraine without aura (MWoA). Forty patients with MWoA were divided into two groups according to their self‐rating depression scale (SDS) score in the present study, including 20 in the SDS (+) (SDS > 49) group and 20 in the SDS (−) (SDS ≤ 49) group. Forty healthy participants were also recruited as the control group. Tract‐based spatial statistics analyses with multiple diffusion tensor imaging‐derived indices [fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), axial diffusivity (AD)] were employed collectively to investigate WM integr...
J‐refocused 1H PRESS DEPT for localized 13C MR Spectroscopy
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Proton point‐resolved spectroscopy (PRESS) localization has been combined with distortionless enhanced polarization transfer (DEPT) in multinuclear MRS to overcome the signal contamination problem in image‐selected in vivo spectroscopy (ISIS)‐combined DEPT, especially for lipid detection. However, homonuclear proton scalar couplings reduce the DEPT enhancement by modifying the spin coherence distribution under J modulation during proton PRESS localization. Herein, a J‐refocused proton PRESS‐localized DEPT sequence is presented to obtain simultaneously enhanced and localized signals from a large number of metabolites by in vivo 13C MRS. The suppression of J modulation during PRESS and the substantial recovery of signal enhancement by J‐refocused PRESS‐localized DEPT were demon...
Three‐dimensional mapping of the creatine kinase enzyme reaction rate in muscles of the lower leg
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In this study, we developed and implemented at ultra‐high field (7T) a novel three‐dimensional 31P‐MT imaging sequence that maps the kinetics of CK in the entire volume of the lower leg at relatively high resolution (0.52 mL voxel size), and within acquisition times that can be tolerated by patients (below 60 min). We tested the sequence on five healthy and two clinically diagnosed type 2 diabetic subjects. Overall, we obtained measurements that are in close agreement with measurements reported previously using spectroscopic methods. Importantly, our spatially resolved method allowed us to measure local CK reaction rate constants and metabolic fluxes in individual muscles in a non‐invasive manner. Furthermore, it allowed us to detect variations of the CK rates of different muscles,...
Gaussian mixture model‐based classification of dynamic contrast enhanced MRI data for identifying diverse tumor microenvironments: preliminary results
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In this study, DCE‐MRI data from a rat prostate tumor model were analysed with a Gaussian mixture model (GMM)‐based classification to identify perfused, hypoxic and necrotic areas for a total of ten tumor slices from six rats, of which one slice was used as training data for GMM classifications. The results of pattern recognition analyzes were validated by comparison to corresponding Akep maps defining the perfused area (0.84 ± 0.09 overlap), hematoxylin and eosin (H&E)‐stained tissue sections defining necrosis (0.64 ± 0.15 overlap) and pimonidazole‐stained sections defining hypoxia (0.72 ± 0.17 overlap), respectively. Our preliminary data indicate the feasibility of a GMM‐based classification to identify tumor hypoxia, necrosis and perfusion/permeability from ...
Anteroposterior perfusion heterogeneity in human hippocampus measured by arterial spin labeling MRI
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Measurements of blood flow in the human hippocampus are complicated by its relatively small size, unusual anatomy and patterns of blood supply. Only a handful of arterial spin labeling (ASL) MRI articles have reported regional cerebral blood flow (rCBF) values for the human hippocampus. Numerous reports have found heterogeneity in a number of other physiological and biochemical parameters along the longitudinal hippocampal axis. There is, however, only one ASL study of perfusion properties as a function of anteroposterior location in the hippocampus, reporting that rCBF is lower and the arterial transit time (ATT) is longer in the anterior hippocampus than in the posterior hippocampus of the rat brain. The purpose of this article was to measure ATT and rCBF in anterior, middle and posterio...
Global gray and white matter metabolic changes after simian immunodeficiency virus infection in CD8‐depleted rhesus macaques: proton MRS imaging at 3 T
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To test the hypotheses that global decreased neuro‐axonal integrity reflected by decreased N‐acetylaspartate (NAA) and increased glial activation reflected by an elevation in its marker, the myo‐inositol (mI), present in a CD8‐depleted rhesus macaque model of HIV‐associated neurocognitive disorders. To this end, we performed quantitative MRI and 16 × 16 × 4 multivoxel proton MRS imaging (TE/TR = 33/1400 ms) in five macaques pre‐ and 4–6 weeks post‐simian immunodeficiency virus infection. Absolute NAA, creatine, choline (Cho), and mI concentrations, gray and white matter (GM and WM) and cerebrospinal fluid fractions were obtained. Global GM and WM concentrations were estimated from 224 voxels (at 0.125 cm3 spatial resolution over ~35% of the brain) using ...
Bilateral substantia nigra and pyramidal tract changes following experimental intracerebral hemorrhage: an MR diffusion tensor imaging study
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This study examined longitudinally both contralateral and ipsilateral SN and PY changes following experimental ICH with diffusion tensor imaging (DTI) and histology. ICH was induced in 14 Sprague‐Dawley rats by the infusion of collagenase into the right striatum. Four‐shot, spin‐echo, echo‐planar DTI was performed at 7 T with a b value of 1000 s/mm2 and 30 diffusion gradient directions at 3.5 h and days 1, 3, 7, 14, 42 and 120 after ICH. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (λ//) and radial diffusivity (λ┴) were measured in SN and PY accordingly. Two to three rats were sacrificed at days 3, 7, 42 and 120 for histology. The contralateral SN showed an increase in λ// with perivascular enlargement during the first 3 days after ICH. The ipsi...
Characterisation of mobile lipid resonances in tissue biopsies from patients with cervical cancer and correlation with cytoplasmic lipid droplets
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The aims of this study were to characterise the major saturated and unsaturated lipid peaks in histologically normal cervical epithelium and stroma, dysplastic epithelium (low‐grade cervical intraepithelial neoplasia, CIN) and cancer‐containing tissue samples from patients with cervical cancer using diffusion‐weighted 1H high‐resolution magic angle spinning MRS, to determine whether mobile lipid resonances (MLRs) distinguish tissue types and to test for a correlation between MLRs and the number of cytoplasmic lipid droplets. Diffusion‐weighted spectra of tissue biopsies were acquired using a stimulated echo sequence with bipolar gradients. Major saturated and unsaturated MLRs were identified and multivariate analysis of peak combinations was used to determine the best separation ...
Assessment of PDA shunt and systemic blood flow in newborns using cardiac MRI
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We present a method to quantify ductal shunt volume and its impact on systemic blood flow in newborns using Phase Contrast MRI, with scope to investigate the history of the duct and aid future clinical trials. (Source: NMR in Biomedicine)
Quantification of the neurochemical profile using simulated macromolecule resonances at 3 T
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The broad resonances underlying the entire 1H NMR spectrum of the brain, ascribed to macromolecules, can influence metabolite quantification. At the intermediate field strength of 3 T, distinct approaches for the determination of the macromolecule signal, previously used at either 1.5 or 7 T and higher, may become equivalent. The aim of this study was to evaluate, at 3 T for healthy subjects using LCModel, the impact on the metabolite quantification of two different macromolecule approaches: (i) experimentally measured macromolecules; and (ii) mathematically estimated macromolecules. Although small, but significant, differences in metabolite quantification (up to 23% for glutamate) were noted for some metabolites, 10 metabolites were quantified reproducibly with both approaches with ...
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No abstract is available for this article. (Source: NMR in Biomedicine)
A dual‐tuned transceive resonator for 13C{1H} MRS: two open coils in one
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Proton‐decoupled, 13C nuclear MRS experiments require a RF coil that operates at the Larmor frequencies of both 13C and 1H. In this work, we designed, built and tested a single‐unit, dual‐tuned coil based on a half‐birdcage open coil design. It was constructed as a low‐pass network with a resonant trap in series with each leg. Traps are tuned in alternate legs such that the two resonant modes arise from currents on alternate legs. The coil performance was compared with that of a dual‐tuned coil consisting of two proton surface coils operating in quadrature and a single surface coil for 13C transmission and reception. The half‐birdcage coil was shown to produce a more homogeneous RF field at each frequency and was more sensitive to a 13C signal arising from regions further fro...
Clinical applications of arterial spin labeling
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MR arterial spin labeling is primarily applied as a neuroimaging method to measure cerebral blood flow. As this technique becomes more widely available, a basic understanding of the clinical applications is necessary for optimal utilization in the setting of patient care. This review focuses on the use of arterial spin labeling imaging for the evaluation of cerebrovascular disease, brain tumors and neuropsychiatric illness. Copyright © 2013 John Wiley & Sons, Ltd. MR arterial spin labeling is primarily applied as a neuroimaging method to measure cerebral blood flow. As this technique becomes more widely available, a basic understanding of the clinical applications is necessary for optimal utilization in the setting of patient care. This review focuses on the use of arterial spin label...
Lithium compartmentation in brain by 7Li MRS: effect of total lithium concentration
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In previous work at 4.7 T, the individual components of biexponential 7Li transverse (T2) spin relaxation in rat brain in vivo were tentatively identified with intra‐ and extracellular Li. The goal in this work was to estimate Li's compartmental distribution as a function of total Li concentration in brain from the biexponential decays. Here a localized, biexponential 7Li T2 MR spin‐relaxation study with isotopically enriched 7LiCl is reported in rat brain in vivo at 7 T. Additionally, a simple linear interpolation using the biexponential T2 values to estimate intracellular Li from individual monoexponential T2 decays was assessed. Intracellular T2 was 14.8 ± 4.3 ms and extracellular T2 was 295 ± 61 ms. The fraction of intracellular brain Li ranged from 37.3 to 64.8% ...
Application of sodium triple‐quantum coherence NMR spectroscopy for the study of growth dynamics in cartilage tissue engineering
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We studied the tissue growth dynamics of tissue‐engineered cartilage at an early growth stage after cell seeding for four weeks using sodium triple‐quantum coherence NMR spectroscopy. The following tissue‐engineering constructs were studied: 1) bovine chondrocytes cultured in alginate beads; 2) bovine chondrocytes cultured as pellets (scaffold‐free chondrocyte pellets); and 3) human marrow stromal cells (HMSCs) seeded in collagen/chitosan based biomimetic scaffolds. We found that the sodium triple‐quantum coherence spectroscopy could differentiate between different tissue‐engineered constructs and native tissues based on the fast and slow components of relaxation rate as well as on the average quadrupolar coupling. Both fast (Tf) and slow (Ts) relaxation times were found to be ...
MRI of carriers of the apolipoprotein E e4 allele–evidence for structural differences in normal‐appearing brain tissue in e4+ relative to e4– young adults
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We present the first study to show subtle differences in the brains of young healthy adult e4+ and e4– subpopulations. These differences were detected in normal‐appearing brain tissue using a range of sophisticated and novel structural imaging techniques. We suggest that such subtle differences in white matter integrity may confer neural efficiency advantages, and hence give rise to the performance differences in tests of verbal fluency. (Source: NMR in Biomedicine)
Noninvasive functional imaging of cerebral blood volume with vascular‐space‐occupancy (VASO) MRI
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Functional MRI (fMRI) based on changes in cerebral blood volume (CBV) can probe directly vasodilatation and vasoconstriction during brain activation or physiologic challenges, and can provide important insights into the mechanism of blood oxygenation level‐dependent (BOLD) signal changes. At present, the most widely used CBV fMRI technique in humans is called vascular‐space‐occupancy (VASO) MRI, and this article provides a technical review of this method. VASO MRI utilizes T1 differences between blood and tissue to distinguish between these two compartments within a voxel, and employs a blood‐nulling inversion recovery sequence to yield an MR signal proportional to 1 – CBV. As such, vasodilatation will result in a VASO signal decrease and vasoconstriction will have the reverse ef...
Genetic tools to manipulate MRI contrast
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Advances in molecular biology in the early 1970s revolutionized research strategies for the study of complex biological processes, which, in turn, created a high demand for new means to visualize these dynamic biological changes noninvasively and in real time. In this respect, MRI was a perfect fit, because of the versatile possibility to alter the different contrast mechanisms. Genetic manipulations are now being translated to MRI through the development of reporters and sensors, as well as the imaging of transgenic and knockout mice. In the past few years, a new molecular biology toolset, namely optogenetics, has emerged, which allows for the manipulation of cellular behavior using light. This technology provides a few particularly attractive features for combination with newly developed...
Magnetic resonance imaging of time‐varying magnetic fields from therapeutic devices
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This article presents the theory behind the method and provides proof of concept by imaging time‐varying magnetic fields generated by a figure‐eight coil inside simple phantoms over a range of frequencies and intensities using a 7T small animal MRI scanner. The method was able to reconstruct the three‐dimensional components of the oscillating magnetic field vector. Copyright © 2013 John Wiley & Sons, Ltd. A method for imaging time‐varying magnetic fields such as those generated by transcranial magnetic stimulators and radiofrequency hyperthermia probes was introduced in this study. The method was able to reconstruct the three‐dimensional components of the oscillating magnetic field vector. Proof of concept was provided by imaging time‐varying magnetic fields generated by a...
Longitudinal evaluation of hepatic lipid deposition and composition in ob/ob and ob/+ control mice
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The objective of this study was to quantitatively assess lipid deposition (fractional lipid mass, fLM) and composition (fraction of polyunsaturated lipids, fPUL and mean chain length, MCL) in livers of ob/ob mice, a genetic model of obesity and mild diabetes, and ob/+ heterozygous control animals in a noninvasive manner using 1H‐MRS at 9.4T. For accurate quantification, intensity values were corrected for differences in T2 values while T1 effects were considered minimal due to the long TR values used. Values of fLM, fPUL and MCL were derived from T2‐corrected signal intensities of lipids and water resonance. Hepatic lipid signals were compared with fasted plasma insulin, glucose and lipid levels. Statistically significant correlations between fPUL and fasting plasma insulin/glucose lev...
Improved Bloch‐Siegert based B1 mapping by reducing off‐resonance shift
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This article is a U.S. Government work and is in the public domain in the USA. The B1+ mapping method on the Bloch‐Siegert (BS) shift is currently limited by tissue heating associated with the BS irradiation pulse. We investigated the possibility of lowering the off‐resonance frequency of this pulse, as the sensitivity of BS‐based B1+ mapping can be substantially improve when irradiating closer to resonance. Using optimized irradiation pulse shape and gradient crusher to minimize direct excitation effects, in vivo experiments on human brain at 7T confirmed the improved sensitivity. (Source: NMR in Biomedicine)
Water signal attenuation by D2O infusion as a novel contrast mechanism for 1H perfusion MRI
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In this study, we propose a contrast‐enhanced strategy to indirectly trace administered D2O by monitoring the signal attenuation of 1H MRI. Experiments on D2O concentration phantoms and in vivo rat brains were conducted to prove the concept of the proposed contrast mechanism. An average maximum signal drop ratio of 5.25 ± 0.91% was detected on 1H MR images of rat brains with 2 mL of D2O administered per 100 g of body weight. As a diffusible tracer for perfusion, D2O infusion is a practicable method for the assessment of tissue perfusion and has the potential to provide different information from gadolinium‐based contrast agents, which have limited permeability for blood vessels. Furthermore, the observed negative relaxivities of D2O reveal the 1H–D exchange effect. Therefore, ap...
Nuclear magnetic resonance imaging of tumour growth and neovasculature performance in vivo reveals Grb7 as a novel antiangiogenic target
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We report that a calmodulin‐binding domain (CaM‐BD) deletion mutant of the growth factor receptor bound protein 7 (Grb7) (denoted Grb7Δ) impairs tumour growth and associated angiogenesis in vivo. We implanted glioma C6 cells in rat brains transfected with an enhanced yellow fluorescent protein (EYFP) chimera of Grb7∆, its EYFP‐Grb7 wild type counterpart, and EYFP alone. We systematically followed intracerebral growth of the tumours, their cellularity and the functional performance of tumour‐associated microvasculature using magnetic resonance imaging, including anatomical T1W and T2W images and functional diffusion and perfusion parameters. Tumours grown from implanted C6 cells expressing EYFP‐Grb7Δ developed slower, became smaller and presented lower apparent cellularity tha...
Alterations of regional spontaneous neuronal activity and corresponding brain circuit changes during resting state in migraine without aura
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Although previous resting‐state studies have reported abnormal functional cerebral changes in patients with migraine without aura (MwoA), few have focused on alterations in both regional spontaneous neuronal activity and corresponding brain circuits in MwoA patients during rest. Eighteen MwoA patients and 18 age‐ and gender‐matched healthy controls (HC) were recruited in the current study. Baseline cerebral alterations were investigated using amplitude of low‐frequency fluctuation (ALFF) and region of interest (ROI)‐based functional connectivity (FC) analyses. Compared with HC, MwoA patients showed decreased ALFF values in the left rostral anterior cingulate cortex (rACC) and bilateral prefrontal cortex (PFC) as well as increased ALFF values in the right thalamus. FC analysis als...
Altered functional brain networks in Prader–Willi syndrome
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Prader–Willi syndrome (PWS) is a genetic imprinting disorder characterized mainly by hyperphagia and early childhood obesity. Previous functional neuroimaging studies used visual stimuli to examine abnormal activities in the eating‐related neural circuitry of patients with PWS. It was found that patients with PWS exhibited both excessive hunger and hyperphagia consistently, even in situations without any food stimulation. In the present study, we employed resting‐state functional MRI techniques to investigate abnormal brain networks related to eating disorders in children with PWS. First, we applied amplitude of low‐frequency fluctuation analysis to define the regions of interest that showed significant alterations in resting‐state brain activity levels in patients compared with ...
Quantification of microvascular cerebral blood flux and late‐stage tumor compartmentalization in 9L gliosarcoma using flow enhanced MRI
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Measurements of tumor microvasculature are important to obtain an understanding of tumor angiogenesis and for the evaluation of therapies. In this work, we characterize the evolution of the microvascular flux at different stages of tumor growth in the 9L rat brain tumor model. The absolute quantification of cerebral blood flux is achieved with MRI at 7 T using the flow enhanced signal intensity (FENSI) method. FENSI flux maps were obtained between 5 and 14 days after glioma cell inoculation. Based on cerebral blood flux maps, we highlighted two main stages of tumor growth, below and above 3 mm, presenting distinct flux patterns and vascular properties. No significant difference emerged from the group analysis performed on the data collected at an early developmental stage (tumor size <...
Longitudinal 1H MRS of rat forebrain from infancy to adulthood reveals adolescence as a distinctive phase of neurometabolite development
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This study represents the first longitudinal, within‐subject 1H MRS investigation of the developing rat brain spanning infancy, adolescence and early adulthood. We obtained neurometabolite profiles from a voxel located in a central location of the forebrain, centered on the striatum, with smaller contributions for the cortex, thalamus and hypothalamus, on postnatal days 7, 35 and 60. Water‐scaled metabolite signals were corrected for T1 effects and quantified using the automated processing software LCModel, yielding molal concentrations. Our findings indicate age‐related concentration changes in N‐acetylaspartate + N‐acetylaspartylglutamate, myo‐inositol, glutamate + glutamine, taurine, creatine + phosphocreatine and glycerophosphocholine + phosphocholine. Using...
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No abstract is available for this article. (Source: NMR in Biomedicine)
Inorganic nanocrystals as contrast agents in MRI: synthesis, coating and introduction of multifunctionality
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Inorganic nanocrystals have myriad applications in medicine, including their use as drug or gene delivery complexes, therapeutic hyperthermia agents, in diagnostic systems and as contrast agents in a wide range of medical imaging techniques. In MRI, nanocrystals can produce contrast themselves, with iron oxides having been the most extensively explored, or can be given a coating that generates MR contrast, for example gold nanoparticles coated with gadolinium chelates. These MR‐active nanocrystals can be used for imaging of the vasculature, liver and other organs, as well as molecular imaging, cell tracking and theranostics. As a result of these exciting applications, the synthesis and rendering of these nanocrystals as water soluble and biocompatible are therefore highly desirable. We d...
Pain response measured with arterial spin labeling
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In this study, we assessed the pain response in the brain using a pulsed‐continuous arterial spin labeling (pCASL) approach and a thermal stimulation paradigm. Using pCASL, response to noxious stimulation was detected in somatosensory cortex, anterior cingulate cortex, anterior insula, hippocampus, amygdala, thalamus and precuneus, consistent with the pain response activation patterns detected using the BOLD imaging approach. We suggest that pCASL is a reliable alternative for functional MRI pain studies in conditions in which blood flow, volume or oxygen extraction are altered or compromised. Copyright © 2013 John Wiley & Sons, Ltd. Pulsed‐continuous arterial spin labeling was successfully used in a functional MRI study assessing brain response to noxious stimulation. Activation ...
Reliability and spatial specificity of rat brain sensorimotor functional connectivity networks are superior under sedation compared with general anesthesia
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In this study, we investigated rat brain connectivity networks under 1.5% isoflurane anesthesia in comparison with medetomidine sedation. rsfMRI data were acquired under both anesthesia conditions within one imaging session. Male Wistar rats (n = 17) were scanned at 11.7 T with focus on the sensorimotor system. The data underwent a per‐subject independent component analysis (ICA), after which individual components were grouped using hierarchical clustering. Consistent and reliable networks were identified under medetomidine in sensorimotor cortex (three networks) and striatum (two networks). The incidence of these networks was drastically reduced under isoflurane. Seed correlation analysis confirmed these results and revealed globally elevated correlations with low topical specificit...
Nuts and bolts of chemical exchange saturation transfer MRI
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Chemical exchange saturation transfer (CEST) has emerged as a novel MRI contrast mechanism that is well suited for molecular imaging studies. This new mechanism can be used to detect small amounts of contrast agent through the saturation of rapidly exchanging protons on these agents, allowing a wide range of applications. CEST technology has a number of indispensable features, such as the possibility of simultaneous detection of multiple ‘colors’ of agents and of changes in their environment (e.g. pH, metabolites, etc.) through MR contrast. Currently, a large number of new imaging schemes and techniques are being developed to improve the temporal resolution and specificity and to correct for the influence of B0 and B1 inhomogeneities. In this review, the techniques developed over the l...
Qualitative and quantitative ultrashort‐TE MRI of cortical bone
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Osteoporosis causes over 1.5 million fractures per year, costing about $15 billion annually in the USA. Current guidelines utilize bone mineral density (BMD) to assess fracture risk; however, BMD alone only accounts for 30–50% of fractures. The other two major components of bone, organic matrix and water, contribute significantly to bone mechanical properties, but cannot be assessed with conventional imaging techniques in spite of the fact that they make up about 57% of cortical bone by volume. Conventional clinical MRI usually detects signals from water in tissues without difficulty, but cannot detect the water bound to the organic matrix, or the free water in the microscopic pores of the Haversian and the lacunar‐canalicular system of cortical bone, because of their very short appare...
In vivo magnetic resonance spectroscopy detection of combined glutamate‐glutamine in healthy upper cervical cord at 3 T
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This study proposed a clinically feasible MRS method for Glx detection in the human cervical cord in vivo including sample sizes needed for conclusive clinical studies. Copyright © 2012 John Wiley & Sons, Ltd. This study takes on the exciting challenge of quantitative measurements of the Glutamate/Glutamine complex (Glx) in the healthy cervical cord by 1 H MRS at 3T. A comparison of short TE PRESS and STEAM sequences was undertaken in vivo for Glx detection. The results infer an easily translatable MRS method for Glx detection in the human cervical cord. This forms a crucial stage in spinal cord MRS, and has important implications for studying mechanisms of neurodegeneration and spinal cord injury. (Source: NMR in Biomedicine)
In vivo magnetic resonance spectroscopy detection of combined glutamate‐glutamine in a healthy upper cervical cord at 3 T
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This study proposed a clinically feasible MRS method for Glx detection in the human cervical cord in vivo including sample sizes needed for conclusive clinical studies. Copyright © 2012 John Wiley & Sons, Ltd. This study takes on the exciting challenge of quantitative measurements of the Glutamate/Glutamine complex (Glx) in the healthy cervical cord by 1 H MRS at 3T. A comparison of short TE PRESS and STEAM sequences was undertaken in vivo for Glx detection. The results infer an easily translatable MRS method for Glx detection in the human cervical cord. This forms a crucial stage in spinal cord MRS, and has important implications for studying mechanisms of neurodegeneration and spinal cord injury. (Source: NMR in Biomedicine)
Exchange‐dependent relaxation in the rotating frame for slow and intermediate exchange – modeling off‐resonant spin‐lock and chemical exchange saturation transfer
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Chemical exchange observed by NMR saturation transfer (CEST) and spin‐lock (SL) experiments provide an MRI contrast by indirect detection of exchanging protons. The determination of the relative concentrations and exchange rates is commonly achieved by numerical integration of the Bloch–McConnell equations. We derive an analytical solution of the Bloch–McConnell equations that describes the magnetization of coupled spin populations under radiofrequency irradiation. As CEST and off‐resonant SL are equivalent, their steady‐state magnetization and dynamics can be predicted by the same single eigenvalue: the longitudinal relaxation rate in the rotating frame R1ρ. For the case of slowly exchanging systems, e.g. amide protons, the saturation of the small proton pool is affected by tra...
Spatially matched in vivo and ex vivo MR metabolic profiles of prostate cancer – investigation of a correlation with Gleason score
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The objective of this study was to assess the relationship between the Gleason score and the metabolic biomarker (choline + creatine + spermine)/citrate (CCS/C) measured by ex vivo high‐resolution magic angle spinning MRS (HR‐MAS MRS) and in vivo MRSI, and to evaluate the correlation between in vivo‐ and ex vivo‐measured metabolite ratios from spatially matched prostate regions. Patients (n = 13) underwent in vivo MRSI prior to radical prostatectomy. A prostate tissue slice was snap‐frozen shortly after surgery and the locations of tissue samples (n = 40) collected for ex vivo HR‐MAS were matched to in vivo MRSI voxels (n = 40). In vivo MRSI was performed on a 3T clinical MR system and ex vivo HR‐MAS on a 14.1T magnet. Relative metabolite concentrations were calcu...
Referee acknowledgements
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(Source: NMR in Biomedicine)
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No abstract is available for this article. (Source: NMR in Biomedicine)
Diffusion of hyperpolarized 13C‐metabolites in tumor cell spheroids using real‐time NMR spectroscopy
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The detection of tumors noninvasively, the characterization of their progression by defined markers and the monitoring of response to treatment are goals of medical imaging techniques. In this article, a method which measures the apparent diffusion coefficients (ADCs) of metabolites using hyperpolarized 13C diffusion‐weighted spectroscopy is presented. A pulse sequence based on the pulsed gradient spin echo (PGSE) was developed that encodes both kinetics and diffusion information. In experiments with MCF‐7 human breast cancer cells, we detected an ADC of intracellularly produced lactate of 1.06 ± 0.15 µm2/ms, which is about one‐half of the value measured with pyruvate in extracellular culture medium. When monitoring tumor cell spheroids during progressive membrane permeabiliz...
Quantitative comparison of post‐processing methods for reduction of frequency modulation sidebands in non‐water suppression 1H MRS
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In this study, we propose two algorithms based on advanced matrix decomposition to remove the FM sidebands. These methods, the simultaneous diagonalization (QZ) algorithm and its subsequent variant, the simultaneously generalized Schur decomposition (SGSD) algorithm, were numerically evaluated using computer simulations. In addition, we quantitatively compared the performance of these methods and the modulus method in an in vitro experiment and in vivo NWS MRS against conventional WS data. Our results show that the proposed SGSD algorithm can reduce the FM sidebands to achieve superior estimation of concentration on three major metabolites. This method can be applied directly to spectra pre‐acquired under various experimental conditions without modifying the acquisition sequences. Copyri...
In vivo measurement of aldehyde dehydrogenase‐2 activity in rat liver ethanol model using dynamic MRSI of hyperpolarized [1‐13C]pyruvate
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To date, measurements of the activity of aldehyde dehydrogenase‐2 (ALDH2), a critical mitochondrial enzyme for the elimination of certain cytotoxic aldehydes in the body and a promising target for drug development, have been largely limited to in vitro methods. Recent advancements in MRS of hyperpolarized 13C‐labeled substrates have provided a method to detect and image in vivo metabolic pathways with signal‐to‐noise ratio gains greater than 10 000‐fold over conventional MRS techniques. However aldehydes, because of their toxicity and short T1 relaxation times, are generally poor targets for such 13C‐labeled studies. In this work, we show that dynamic MRSI of hyperpolarized [1‐13C]pyruvate and its conversion to [1‐13C]lactate can provide an indirect in vivo measurement of...
Increased interhemispheric resting‐state functional connectivity in functional dyspepsia: a pilot study
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This study examined the interhemispheric resting‐state functional connectivity (RSFC) changes in patients with functional dyspepsia (FD) using functional MRI (fMRI). It was found that patients with FD had elevated global interhemispheric RSFC when compared with healthy controls (HCs). Voxelwise analysis revealed that patients with FD had higher interhemispheric RSFC than HCs in multiple brain regions, including the anterior cingulate cortex (ACC), insula (INS) and thalamus (THAL). (Source: NMR in Biomedicine)
Intravascular contrast agent T2* relaxivity in brain tissue
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In this study, we empirically tested a non‐linear expression based on static dephasing regime (SDR) and linear approximation. Signal‐time curves in white (WM) and grey matter (GM) were converted to concentration time curves (CTCs) using both expressions. Parameters for both linear and non‐linear formulations were adjusted to give a best agreement between cerebral blood volumes (CBV) calculated from WM and arterial CTCs in a group of normal subjects scanned at 3T. Optimized parameters were used to calculate blood volume in WM and GM in healthy subjects scanned at 3T and in meningioma patients scanned at 1.5T. Results from this study showed that a non‐linear SDR formulation gave an acceptable functional form for tissue relaxivity, giving reliable CBV estimates at different field stre...
The evolution of traumatic brain injury in a rat focal contusion model
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This article is a US Government work and is in the public domain in the USA. Lesion evolution was investigated by MRI in a rat model of traumatic brain injury. Serial MRI of cortical lesions demonstrated a high degree of variability in lesions over time, and evolving lesion‐related hemorrhage was observed between days 2 and 9. Serial MRI plus endpoint analysis can yield a greater understanding of injury evolution. (Source: NMR in Biomedicine)
MRI reporter genes: applications for imaging of cell survival, proliferation, migration and differentiation
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Molecular imaging strives to detect molecular events at the level of the whole organism. In some cases, the molecule of interest can be detected either directly or with targeted contrast media. However many genes and proteins and particularly those located in intracellular compartments are not accessible for targeted agents. The transcriptional regulation of these genes can nevertheless be detected, although indirectly, using reporter gene encoding for readily detectable proteins. Such reporter proteins can be expressed in the tissue of interest by genetically introducing the reporter gene in the target cells. Imaging of reporter genes has become a powerful tool in modern biomedical research. Typically, expression of fluorescent and bioluminescent proteins and the reaction product of expre...
Diffusion tensor imaging and T2 relaxometry of bilateral lumbar nerve roots: feasibility of in‐plane imaging
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Cerebral blood volume MRI with intravascular superparamagnetic iron oxide nanoparticles
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The cerebral blood volume (CBV) is a crucial physiological indicator of tissue viability and vascular reactivity. Thus, noninvasive CBV mapping has been of great interest. For this, ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles, including monocrystalline iron oxide nanoparticles, can be used as long‐half‐life, intravascular susceptibility agents of CBV MRI measurements. Moreover, CBV‐weighted functional MRI (fMRI) with USPIO nanoparticles provides enhanced sensitivity, reduced large vessel contribution and improved spatial specificity relative to conventional blood oxygenation level‐dependent fMRI, and measures a single physiological parameter that is easily interpretable. We review the physiochemical and magnetic properties, and pharmacokinetics, of USPIO nanoparti...
Extracting MRS discriminant functional features of brain tumors
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The current challenge in automatic brain tumor classification based on MRS is the improvement of the robustness of the classification models that explicitly account for the probable breach of the independent and identically distributed conditions in the MRS data points. To contribute to this purpose, a new algorithm for the extraction of discriminant MRS features of brain tumors based on a functional approach is presented. Functional data analysis based on region segmentation (RSFDA) is based on the functional data analysis formalism using nonuniformly distributed B splines according to spectral regions that are highly correlated. An exhaustive characterization of the method is presented in this work using controlled and real scenarios. The performance of RSFDA was compared with other wide...
Microencapsulated cell tracking
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Microencapsulation of therapeutic cells has been widely pursued to achieve cellular immunoprotection following transplantation. Initial clinical studies have shown the potential of microencapsulation using semi‐permeable alginate layers, but much needs to be learned about the optimal delivery route, in vivo pattern of engraftment, and microcapsule stability over time. In parallel with noninvasive imaging techniques for ‘naked’ (i.e. unencapsulated) cell tracking, microcapsules have now been endowed with contrast agents that can be visualized by 1H MRI, 19F MRI, X‐ray/computed tomography and ultrasound imaging. By placing the contrast agent formulation in the extracellular space of the hydrogel, large amounts of contrast agents can be incorporated with negligible toxicity. This has ...
Regional specificity of manganese accumulation and clearance in the mouse brain: implications for manganese‐enhanced MRI
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Manganese‐enhanced MRI has recently become a valuable tool for the assessment of in vivo functional cerebral activity in animal models. As a result of the toxicity of manganese at higher dosages, fractionated application schemes have been proposed to reduce the toxic side effects by using lower concentrations per injection. Here, we present data on regional‐specific manganese accumulation during a fractionated application scheme over 8 days of 30 mg/kg MnCl2, as well as on the clearance of manganese chloride over the course of several weeks after the termination of the whole application protocol supplying an accumulative dose of 240 mg/kg MnCl2. Our data show most rapid accumulation in the superior and inferior colliculi, amygdala, bed nucleus of the stria terminalis, cornu ammon...
Classification of breast lesions pre‐contrast injection using water resonance lineshape analysis
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Inhomogeneously broadened, non‐Lorentzian water resonances have been observed in small image voxels of breast tissue. The non‐Lorentzian components of the water resonance are probably produced by bulk magnetic susceptibility shifts caused by dense, deoxygenated tumor blood vessels (the ‘blood oxygenation level‐dependent’ effect), but can also be produced by other characteristics of local anatomy and physiology, including calcifications and interfaces between different types of tissue. Here, we tested the hypothesis that the detection of non‐Lorentzian components of the water resonance with high spectral and spatial resolution (HiSS) MRI allows the classification of breast lesions without the need to inject contrast agent. Eighteen malignant lesions and nine benign lesions were ...
MRI tracking of transplanted iron‐labeled mesenchymal stromal cells in an immune‐compromised mouse model of critical limb ischemia
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In this study, a severely immune‐compromised mouse, with limited macrophage activity, was investigated to examine cell tracking in a system in which bystander cell uptake of dead, iron‐labeled cells or free iron particles was minimized. MRI was used to track the fate of MSCs over 21 days after their intramuscular transplantation in mice with a femoral artery ligation. In all mice, a region of signal loss was observed at the injection site and the volume of signal hypointensity diminished over time. Fluorescence and light microscopy showed that iron‐positive MSCs persisted at the transplant site and often appeared to be integrated in perivascular niches. This was compared with MSC transplantation in immune‐competent mice with femoral artery ligation. In these mice, the regions of ...
Accelerated high‐frame‐rate mouse heart cine‐MRI using compressed sensing reconstruction
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We introduce a new protocol to obtain very high‐frame‐rate cinematographic (Cine) MRI movies of the beating mouse heart within a reasonable measurement time. The method is based on a self‐gated accelerated fast low‐angle shot (FLASH) acquisition and compressed sensi ng reconstruction. Key to our approach is that we exploit the stochastic nature of the retrospective triggering acquisition scheme to produce an undersampled and random k–t space filling that allows for compressed sensing reconstruction and acceleration. As a standard, a self‐gated FLASH sequence with a total acquisition time of 10 min was used to produce single‐slice Cine movies of seven mouse hearts with 90 frames per cardiac cycle. Two times (2×) and three times (3×) k–t space undersampled Cine movies were ...
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No abstract is available for this article. (Source: NMR in Biomedicine)
Regional neonatal brain absolute thermometry by 1H MRS
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This study evaluates the clinical feasibility of MRSt in human neonates, and correlates white matter (WM) and thalamus (Thal) MRSt with conventional rectal temperature (Trectal) measurement. Fifty‐six infants born at term underwent perinatal MRSt for suspected hypoxic–ischaemic brain injury and 33 infants born preterm had MRSt at a term‐equivalent age; 56 of the 89 had Trectal measured after MRSt of either a Thal or posterior WM voxel, or both. MRSt used point‐resolved spectroscopy (no water suppression; TR = 1370 ms; TE = 288 ms; 1.5 × 1.5 × 1.5 cm3 Thal and 1.1 × 1.3 × 1.4 cm3 WM voxels). Time domain data were phase and frequency corrected before summation and motion‐corrupted data were excluded from further analysis using simple criteria [pr...
Analysis of parametric histogram from dynamic contrast‐enhanced MRI: application in evaluating brain tumor response to radiotherapy
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In conclusion, the derived mFWHM reflects tumor heterogeneity, and the ability to depict patient survival probability from TMR corresponds well with that from RECIST. The results reveal that, in brain tumors, progression may be exhibited not only by tumor size, but also by tumor heterogeneity. Copyright © 2012 John Wiley & Sons, Ltd. The modified full width at half‐maximum (mFWHM) calculated from the wash‐in slope histogram is proposed as a parameter for the evaluation of changes in tumor heterogeneity which respond to radiotherapy. Brain tumors were evaluated by mFWHM post‐ to pre‐therapy ratios (defined as the therapeutic mFWHM ratio, TMR). The TMR has the ability to distinguish between nonresponders and responders. The patient survival probability from TMR corresponds well ...
Dynamic three‐dimensional imaging of phosphocreatine recovery kinetics in the human lower leg muscles at 3T and 7T: a preliminary study
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This study focuses on the development and implementation of a spectrally selective three‐dimensional turbo spin echo (3D‐TSE) sequence at 3T and 7T with temporal resolution of 24 s, using two geometrically identical volume coils. We acquired imaging data of PCr recovery from four healthy volunteers and one diabetic patient, who performed plantar flexions using resistance bands. We segmented the anatomical regions of six different muscles from the lower leg, namely the gastrocnemius [lateral (GL) and medial (GM)], the tibialis [anterior (TA) and posterior (TP)], the soleus (S) and the peroneus (P) and measured the local PCr resynthesis rate constants. During the same examination, we also acquired unlocalized 31P‐MRS data at a temporal resolution of 6 s. At 3T, the PCr resynthesis ...
Quantitative analysis of hyperpolarized 129Xe ventilation imaging in healthy volunteers and subjects with chronic obstructive pulmonary disease
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In this study, hyperpolarized 129Xe MR ventilation and 1H anatomical images were obtained from three subject groups: young healthy volunteers (HVs), subjects with chronic obstructive pulmonary disease (COPD) and age‐matched controls (AMCs). Ventilation images were quantified by two methods: an expert reader‐based ventilation defect score percentage (VDS%) and a semi‐automated segmentation‐based ventilation defect percentage (VDP). Reader‐based values were assigned by two experienced radiologists and resolved by consensus. In the semi‐automated analysis, 1H anatomical images and 129Xe ventilation images were both segmented following registration to obtain the thoracic cavity volume and ventilated volume, respectively, which were then expressed as a ratio to obtain the VDP. Venti...
Dynamic monitoring of blood–brain barrier integrity using water exchange index (WEI) during mannitol and CO2 challenges in mouse brain
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The integrity of the blood–brain barrier (BBB) is critical to normal brain function. Traditional techniques for the assessment of BBB disruption rely heavily on the spatiotemporal analysis of extravasating contrast agents. However, such methods based on the leakage of relatively large molecules are not suitable for the detection of subtle BBB impairment or for the performance of repeated measurements in a short time frame. Quantification of the water exchange rate constant (WER) across the BBB using strictly intravascular contrast agents could provide a much more sensitive method for the quantification of the BBB integrity. To estimate WER, we have recently devised a powerful new method using a water exchange index (WEI) biomarker and demonstrated BBB disruption in an acute stroke model....
T2 mapping provides multiple approaches for the characterization of muscle involvement in neuromuscular diseases: a cross‐sectional study of lower leg muscles in 5–15‐year‐old boys with Duchenne muscular dystrophy
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This study shows that T2 mapping provides multiple approaches that can be used effectively to characterize muscle tissue in children with DMD, even in the early stages of the disease. Therefore, T2 mapping may prove to be clinically useful in the monitoring of muscle changes caused by the disease process or by therapeutic interventions in DMD. Copyright © 2012 John Wiley & Sons, Ltd. This study used T2 mapping with and without fat saturation (spectral presaturation with inversion recovery) to measure the involvement of lower leg muscles (a) in unaffected children (b) and in boys with Duchenne muscular dystrophy (DMD) (c) of a variety of ages and disease severities. Muscle mean T2, heterogeneity of T2 values within muscles (d) and the percentage of the area affected (e) were elevated (...
Ultra high spatial and temporal resolution breast imaging at 7T
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There is a need to obtain higher specificity in the detection of breast lesions using MRI. To address this need, Dynamic Contrast‐Enhanced (DCE) MRI has been combined with other structural and functional MRI techniques. Unfortunately, owing to time constraints structural images at ultra‐high spatial resolution can generally not be obtained during contrast uptake, whereas the relatively low spatial resolution of functional imaging (e.g. diffusion and perfusion) limits the detection of small lesions. To be able to increase spatial as well as temporal resolution simultaneously, the sensitivity of MR detection needs to increase as well as the ability to effectively accelerate the acquisition. The required gain in signal‐to‐noise ratio (SNR) can be obtained at 7T, whereas acceleration c...
Composite slice‐selective adiabatic excitation for prostate MRSI
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Higher magnetic field strengths, such as 7 T, offer increased spectral resolution and higher signal‐to‐noise ratio. These properties can be very advantageous for MRSI. In particular, signals that generally overlap at lower fields, such as choline, polyamines and creatine, can be resolved at 7 T. However, higher magnetic field strengths suffer from strong radiofrequency (RF) field nonuniformities. These nonuniformities become even stronger when using surface transceivers, such as an endorectal coil for prostate imaging. In order to obtain uniform excitations for accurate MRSI measurements, adiabatic sequences are therefore recommended. Conventional adiabatic MRS sequences (i.e. localization by adiabatic selective refocusing, LASER) have relatively long TEs, especially when optimized...
Multimodal iron oxide nanoparticles for hybrid biomedical imaging
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Iron oxide core nanoparticles are attractive imaging agents because their material properties allow the tuning of pharmacokinetics as well as the attachment of multiple moieties to their surface. In addition to affinity ligands, these include fluorochromes and radioisotopes for detection with optical and nuclear imaging. As the iron oxide core can be detected by MRI, options for combining imaging modalities are manifold. Already, preclinical imaging strategies have combined noninvasive imaging with higher resolution techniques, such as intravital microscopy, to gain unprecedented insight into steady‐state biology and disease. Going forward, hybrid iron oxide nanoparticles will help to merge modalities, creating a synergy that will enable imaging in basic research and, potentially, also i...
Electrocardiogram‐triggered, higher order, projection‐based B0 shimming allows for fast and reproducible shim convergence in spinal cord 1H MRS
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1H MRS allows insight into the chemical composition of the central nervous system. However, as a result of technical challenges, it has rarely been applied to the spinal cord. In particular, the strong susceptibility changes around the spinal cord and the pulsatile flow of the cerebrospinal fluid lead to distinct B0 field distortions which often considerably degrade the spectral quality. Hence, B0 shimming is one of the main challenges in 1H MRS of the spinal cord. Electrocardiogram (ECG)‐triggered, higher order, projection‐based B0 shimming was introduced and compared with both conventional projection‐based B0 shimming and B0 shimming based on ECG‐triggered, three‐dimensional B0 field mapping. The linewidth of the unsuppressed water peak was used to evaluate the reproducibility ...
Does MPTP intoxication in mice induce metabolite changes in the nucleus accumbens? A 1H nuclear MRS study
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This study was carried out on controls and 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐intoxicated mice. In vivo spectra were acquired for a voxel (8 μL) in the dorsal striatum, and in the NAc (1.56 μL). NMR acquisitions were first performed 10 days after the last MPTP injection in a basal condition [after saline intraperitoneal (i.p.) injection] and then in the same animal the week after basal NMR acquisitions, after acute levodopa administration (200 mg kg–1, i.p.). Immunohistochemistry was used to determine the levels of (Glu) glutamate, glutamine synthetase (GS) and glutamic acid decarboxylase (GAD) isoform 67 in these two structures. The Glu, Gln and GABA concentrations obtained in the basal state were higher in the NAc of MPTP‐intoxicated mice which have the...
Advantages of paramagnetic chemical exchange saturation transfer (CEST) complexes having slow to intermediate water exchange properties as responsive MRI agents
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Paramagnetic chemical exchange saturation transfer (PARACEST) complexes are exogenous contrast agents that have great potential to further extend the functional and molecular imaging capabilities of magnetic resonance. As a result of the presence of a central paramagnetic lanthanide ion (Ln3+ ≠ La3+, Gd3+, Lu3+) within the chelate, the resonance frequencies of exchangeable protons bound to the PARACEST agent are shifted far away from the bulk water frequency. This large chemical shift, combined with an extreme sensitivity to the chemical exchange rate, make PARACEST agents ideally suited for the reporting of significant biological metrics, such as temperature, pH and the presence of metabolites. In addition, the ability to turn PARACEST agents ‘off’ and ‘on’ using a frequency...
Imaging of glutamate neurotransmitter alterations in Alzheimer's disease
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Glutamate (Glu) is a major excitatory neurotransmitter in the brain and has been shown to decrease in the early stages of Alzheimer's disease (AD). Using a glutamate chemical (amine) exchange saturation transfer (GluCEST) method, we imaged the change in [Glu] in the APP‐PS1 transgenic mouse model of AD at high spatial resolution. Compared with wild‐type controls, AD mice exhibited a notable reduction in GluCEST contrast (~30%) in all areas of the brain. The change in [Glu] was further validated through 1H MRS. A positive correlation was observed between GluCEST contrast and 1H MRS‐measured Glu/total creatine ratio. This method potentially provides a novel noninvasive biomarker for the diagnosis of the disease in preclinical stages and enables the development of disease‐modifying th...
NMR of hyperpolarised probes
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Increasing the sensitivity of NMR experiments is an ongoing field of research to help realise the exquisite molecular specificity of this technique. Hyperpolarisation of various nuclei is a powerful approach that enables the use of NMR for molecular and cellular imaging. Substantial progress has been achieved over recent years in terms of both tracer preparation and detection schemes. This review summarises recent developments in probe design and optimised signal encoding, and promising results in sensitive disease detection and efficient therapeutic monitoring. The different methods have great potential to provide molecular specificity not available by other diagnostic modalities. Copyright © 2012 John Wiley & Sons, Ltd. This review summarises recent developments in the use of hyperp...
Strategies for the development of gadolinium‐based ‘q’‐activatable MRI contrast agents
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Hierarchical non‐negative matrix factorization (hNMF): a tissue pattern differentiation method for glioblastoma multiforme diagnosis using MRSI
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MRSI has shown potential in the diagnosis and prognosis of glioblastoma multiforme (GBM) brain tumors, but its use is limited by difficult data interpretation. When the analyzed MRSI data present more than two tissue patterns, conventional non‐negative matrix factorization (NMF) implementation may lead to a non‐robust estimation. The aim of this article is to introduce an effective approach for the differentiation of GBM tissue patterns using MRSI data. A hierarchical non‐negative matrix factorization (hNMF) method that can blindly separate the most important spectral sources in short‐TE 1H MRSI data is proposed. This algorithm consists of several levels of NMF, where only two tissue patterns are computed at each level. The method is demonstrated on both simulated and in vivo short...
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No abstract is available for this article. (Source: NMR in Biomedicine)
Fraction of unsaturated fatty acids in visceral adipose tissue (VAT) is lower in subjects with high total VAT volume – a combined 1H MRS and volumetric MRI study in male subjects
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Visceral adipose tissue (VAT) is thought to play an important role in the pathogenesis of obesity and insulin resistance. However, little is known about the composition of VAT with regard to the amount of mono‐ (MUFAs) and polyunsaturated fatty acids (PUFAs) in triglycerides. Volume‐selective MRS was performed in addition to MRI for the quantification of VAT. Analysis comprised proton signals from the vinyl‐H group (H–C = C–H), including protons from MUFA + PUFA, and diallylic‐H, i.e. methylene‐interrupted PUFAs. The methyl (−CH3) resonance, which is the only peak with a defined number of protons/triglyceride (n = 9), served as reference. Twenty male subjects participated in this prospective study and underwent MRS of VAT on a 3‐T whole‐body unit. Spectra we...
A theoretical and experimental comparison of different techniques for B1 mapping at very high fields
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With the increasing use of ultrahigh‐field MR with multiple transmit channels, mapping of the B1+ field has become a critical factor in many studies, leading to the publication of a large number of sequences for the measurement of the flip angle in recent years. In this article, the accuracy, precision and practicability of some of the most prominent of these techniques are investigated both theoretically, using error propagation computations and Monte‐Carlo simulations, and experimentally for different settings. For an exemplary experiment, which is typical for high‐field applications, the flip angle uncertainty is calculated and measured for two‐ and three‐dimensional acquisitions for techniques based on both magnitude and phase data. Simulated and measured results show good ag...
High‐precision calibration of MRS thermometry using validated temperature standards: effects of ionic strength and protein content on the calibration
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Currently, there is very limited ability to measure the temperature of the brain, but a direct technique for its estimation in vivo could improve the detection of patients at risk of temperature‐related brain damage, help in the diagnosis of stroke and tumour, and provide useful information on the mechanisms of thermoregulation of the brain. In this article, new calibrations in vitro of MRS thermometry using temperature‐stabilised reference phantoms are reported. The phantoms comprise two concentric glass spheres: the inner sphere contains the phantom material to be measured by MRS, and the outer sphere contains a substance with a known temperature stable to within 0.2 °C. The substances were freezing organic fixed‐point compounds (diphenyl ether and ethylene carbonate, freezing at ...
A review of calibrated blood oxygenation level‐dependent (BOLD) methods for the measurement of task‐induced changes in brain oxygen metabolism
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The dynamics of the blood oxygenation level‐dependent (BOLD) response are dependent on changes in cerebral blood flow, cerebral blood volume and the cerebral metabolic rate of oxygen consumption. Furthermore, the amplitude of the response is dependent on the baseline physiological state, defined by the haematocrit, oxygen extraction fraction and cerebral blood volume. As a result of this complex dependence, the accurate interpretation of BOLD data and robust intersubject comparisons when the baseline physiology is varied are difficult. The calibrated BOLD technique was developed to address these issues. However, the methodology is complex and its full promise has not yet been realised. In this review, the theoretical underpinnings of calibrated BOLD, and issues regarding this theory that...
Serial measurement of hepatic lipids during chemotherapy in patients with colorectal cancer: a 1H MRS study
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Hepatic steatosis is a hallmark of chemotherapy‐induced liver injury. We made serial 1H MRS measurements of hepatic lipids in patients over the time course of a 24‐week chemotherapeutic regimen to determine whether 1H MRS could be used to monitor the progression of chemotherapy‐induced steatosis. Thirty‐four patients with stage III or IV colorectal cancer receiving 5‐fluorouracil, folinic acid and oxaliplatin (n = 21) or hepatic arterial infusion of floxuridine with systemic irinotecan (n = 13) were studied prospectively. 1H MRS studies were performed at baseline and after 6 and 24 weeks of treatment. A 1H MR spectrum was acquired from the liver during a breath hold and the ratio of fat to fat + water (FFW) was calculated to give a measure of hepatic triglycerides (...
Combined MR, fluorescence and histology imaging strategy in a human breast tumor xenograft model
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Applications of molecular imaging in cancer and other diseases frequently require the combination of in vivo imaging modalities, such as MR and optical imaging, with ex vivo optical, fluorescence, histology and immunohistochemical imaging to investigate and relate molecular and biological processes to imaging parameters within the same region of interest. We have developed a multimodal image reconstruction and fusion framework that accurately combines in vivo MRI and MRSI, ex vivo brightfield and fluorescence microscopic imaging and ex vivo histology imaging. Ex vivo brightfield microscopic imaging was used as an intermediate modality to facilitate the ultimate link between ex vivo histology and in vivo MRI/MRSI. Tissue sectioning necessary for optical and histology imaging required the ge...
Treatment with the MEK inhibitor U0126 induces decreased hyperpolarized pyruvate to lactate conversion in breast, but not prostate, cancer cells
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In this study, we monitored the effect of treatment with the mitogen‐activated protein kinase (MEK) inhibitor U0126 in prostate and breast cancer cells. Following treatment, we observed a 31% decrease in the flux of hyperpolarized 13C label in treated MCF‐7 breast cancer cells relative to controls. In contrast, and unexpectedly, the flux increased to 167% in treated PC3 prostate cancer cells. To mechanistically explain these observations, we investigated treatment‐induced changes in the different factors known to affect the pyruvate to lactate conversion. NADH (nicotinamide adenine dinucleotide, reduced form) levels remained unchanged, whereas lactate dehydrogenase expression and activity, as well as intracellular lactate, increased in both cell lines, providing an explanation for th...
Cardiac proton spectroscopy using large coil arrays
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Large coil arrays are widely used in clinical routine for cardiovascular imaging providing extended spatial coverage and enabling accelerated acquisition using parallel imaging approaches. This work investigates the use of large coil arrays in single‐voxel cardiac spectroscopy for the detection of myocardial creatine and triglyceride content. For this purpose, a navigator‐gated and cardiac‐triggered point‐resolved spectroscopy sequence was implemented, and data obtained in 11 healthy volunteers using 32‐ and 5‐element coil arrays were compared. For combination of the individual coil element signals, four strategies were evaluated differing in the manner of estimation of the complex coil weights and the amount of additional information required for coil combination. In all volun...
Blood oxygenation level‐dependent functional MRI signal turbulence caused by ultrahigh spatial resolution: numerical simulation and theoretical explanation
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We present a four‐level coarse‐to‐fine multiresolution BOLD fMRI signal simulation. Based on the statistical histogram of an intravoxel fieldmap, we reformulate the intravoxel dephasing summation (a form of Riemann sum) into a new formula that is a discrete Fourier transformation of the intravoxel fieldmap histogram (a form of Lebesgue sum). We interpret the BOLD signal formation by relating its magnitude (phase) to the even (odd) symmetry of the fieldmap histogram. Based on multiresolution BOLD signal simulation, we find that the signal turbulence mainly emerges at the vessel boundary, and that there are only a few voxels (less than 10%) in an ultrahigh‐resolution image that reveal turbulence in the form of sparse point noise. Our simulation also shows that, for typical human brai...
Blood oxygenation level‐dependent (BOLD)‐based techniques for the quantification of brain hemodynamic and metabolic properties – theoretical models and experimental approaches
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The quantitative evaluation of brain hemodynamics and metabolism, particularly the relationship between brain function and oxygen utilization, is important for the understanding of normal human brain operation, as well as the pathophysiology of neurological disorders. It can also be of great importance for the evaluation of hypoxia within tumors of the brain and other organs. A fundamental discovery by Ogawa and coworkers of the blood oxygenation level‐dependent (BOLD) contrast opened up the possibility to use this effect to study brain hemodynamic and metabolic properties by means of MRI measurements. Such measurements require the development of theoretical models connecting the MRI signal to brain structure and function, and the design of experimental techniques allowing MR measurement...
High‐resolution MRI of early‐stage mouse embryos
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Both the availability of methods to manipulate genes and the completion of the mouse genome sequence have led to the generation of thousands of genetically modified mouse lines that provide a new platform for the study of mammalian development and developmental diseases. Phenotyping of mouse embryos has traditionally been performed on fixed embryos by the use of ex vivo histological, optical and high‐resolution MRI techniques. Although potentially powerful, longitudinal imaging of individual animals is difficult or impossible with conventional optical methods because of the inaccessibility of mouse embryos inside the maternal uterus. To address this problem, we present a method of imaging the mouse embryo from stages as early as embryonic day (E)10.5, close to the onset of organogenesis ...
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No abstract is available for this article. (Source: NMR in Biomedicine)
A throughput‐optimized array system for multiple‐mouse MRI
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MRI is a versatile tool for the systematic assessment of anatomical and functional changes in small‐animal models of human disease. Its noninvasive nature makes it an ideal candidate for longitudinal evaluations of disease progression, but relatively long scan times limit the number of observations that can be made in a given interval of time, imposing restrictions on experimental design and potentially compromising statistical power. Methods that reduce the overall time required to scan multiple cohorts of animals in distinct experimental groups are therefore highly desirable. Multiple‐mouse MRI, in which several animals are simultaneously scanned in a common MRI system, has been successfully used to improve study throughput. However, to best utilize the next generation of small‐ani...
A continuous‐flow, high‐throughput, high‐pressure parahydrogen converter for hyperpolarization in a clinical setting
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Pure parahydrogen (pH2) is the prerequisite for optimal pH2‐based hyperpolarization experiments, promising approaches to access the hidden orders of magnitude of MR signals. pH2 production on‐site in medical research centers is vital for the proliferation of these technologies in the life sciences. However, previously suggested designs do not meet our requirements for safety or production performance (flow rate, pressure or enrichment). In this article, we present the safety concept, design and installation of a pH2 converter, operated in a clinical setting. The apparatus produces a continuous flow of four standard liters per minute of ≈98% enriched pH2 at a pressure maximum of 50 bar. The entire production cycle, including cleaning and cooling to 25 K, takes less than 5 h, onl...
Corrigendum
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(Source: NMR in Biomedicine)
Dimethyl sulfoxide (DMSO) as a potential contrast agent for brain tumors
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Dimethyl sulfoxide (DMSO) is commonly used in preclinical studies of animal models of high‐grade glioma as a solvent for chemotherapeutic agents. A strong DMSO signal was detected by single‐voxel MRS in the brain of three C57BL/6 control mice during a pilot study of DMSO tolerance after intragastric administration. This led us to investigate the accumulation and wash‐out kinetics of DMSO in both normal brain parenchyma (n = 3 control mice) by single‐voxel MRS, and in 12 GL261 glioblastomas (GBMs) by single‐voxel MRS (n = 3) and MRSI (n = 9). DMSO accumulated differently in each tissue type, reaching its highest concentration in tumors: 6.18 ± 0.85 µmol/g water, 1.5‐fold higher than in control mouse brain (p < 0.05). A faster wash‐out was detected in...
In vivo MRS and histochemistry of status epilepticus‐induced hippocampal pathology in a juvenile model of temporal lobe epilepsy
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In this study, in vivo MRS was used in a post‐SE juvenile rat model of temporal lobe epilepsy (TLE) to establish the temporal evolution of hippocampal injury and neurotransmitter imbalance. SE was induced in P21 rats by injection of lithium and pilocarpine. Four and eight weeks after SE, in vivo1H and γ‐aminobutyric acid (GABA)‐edited MRS of the hippocampus was performed in combination with dedicated ex vivo immunohistochemistry for the interpretation and validation of MRS findings. MRS showed a 12% decrease (p < 0.0001) in N‐acetylaspartate and a 15% increase (p = 0.0226) in choline‐containing compound concentrations, indicating neuronal death and gliosis, respectively. These results were confirmed by FluoroJade and vimentin staining. Furthermore, severe and progress...
Quality control of prostate 1 H MRSI data
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MRSI of prostate cancer provides a potential clinical tool to aid in the detection and characterisation of this disease, but its clinical use is limited by the need for the specialist training of radiologists to read these datasets. An essential part of this reading is the assessment of the usability and reliability of MRSI spectra because they can be affected by artefacts such as poor signal to noise, lipid signal contamination and broad resonances that could cause errors of interpretation. We have developed an automated quality control algorithm that classifies every voxel of an MRSI dataset as either acceptable or unacceptable for further analysis, based on the spectral profile alone. The method was trained and tested based on a gold standard of agreement of four experts. It was highly ...
Mapping of cerebral perfusion territories using territorial arterial spin labeling: techniques and clinical application
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A knowledge of the exact cerebral perfusion territory which is supplied by any artery is of great importance in the understanding and diagnosis of cerebrovascular disease. The development and optimization of territorial arterial spin labeling (T‐ASL) MRI techniques in the past two decades have made it possible to visualize and determine the cerebral perfusion territories in individual patients and, more importantly, to do so without contrast agents or otherwise invasive procedures. This review provides an overview of the development of ASL techniques that aim to visualize the general cerebral perfusion territories or the territory of a specific artery of interest. The first efforts of T‐ASL with pulsed, continuous and pseudo‐continuous techniques are summarized and subsequent clinica...
Treatment response monitoring in patients with gastrointestinal stromal tumor using diffusion‐weighted imaging: preliminary results in comparison with positron emission tomography/computed tomography
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We compared the parameters derived from diffusion‐weighted imaging (DWI) and positron emission tomography/computed tomography (PET/CT) for treatment response evaluation and response prediction in patients with gastrointestinal stromal tumor (GIST). Seven patients with histologically proven metastatic disease were enrolled. DWI and PET/CT data were collected from all patients at diagnosis and from six at follow‐up. All 37 lesions were identifiable in DWI with a sensitivity of 100%. To achieve higher accuracy, we used the apparent diffusion coefficient (ADC) of liver and background noise as thresholds for the measurement of the ADCs of lesions. Significant inverse correlations were found between ADCmean_thr (ADCmean with thresholds) and SUVmean (mean standardized uptake value) (R2 = ...
The 39 steps: evading error and deciphering the secrets for accurate dynamic susceptibility contrast MRI
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Dynamic susceptibility contrast (DSC) MRI is the most commonly used MRI method to assess cerebral perfusion and other related haemodynamic parameters. Although the technique is well established and used routinely in clinical centres, there are still many problems that impede accurate perfusion quantification. In this review article, we present 39 steps which guide the reader through the theoretical principles, practical decisions, potential problems, current limitations and latest advances in DSC‐MRI. The 39 steps span the collection, analysis and interpretation of DSC‐MRI data, expounding issues and possibilities relating to the contrast agent, the acquisition of DSC‐MRI data, data pre‐processing, the contrast concentration–time course, the arterial input function, deconvolution...
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No abstract is available for this article. (Source: NMR in Biomedicine)
Quantification of glutamate and glutamine using constant‐time point‐resolved spectroscopy at 3 T
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Separate quantification of glutamate (Glu) and glutamine (Gln) using conventional MRS on clinical scanners is challenging. In previous work, constant‐time point‐resolved spectroscopy (CT‐PRESS) was optimized at 3 T to detect Glu, but did not resolve Gln. To quantify Glu and Gln, a time‐domain basis set was constructed taking into account metabolite T2 relaxation times and dephasing from B0 inhomogeneity. Metabolite concentrations were estimated by fitting the basis one‐dimensional CT‐PRESS diagonal magnitude spectra to the measured spectrum. This method was first validated using seven custom‐built phantoms containing variable metabolite concentrations, and then applied to in vivo data acquired in rats exposed to vaporized ethanol and controls. Separate metabolite quantifica...
Response of HT29 colorectal xenograft model to cediranib assessed with 18F‐fluoromisonidazole positron emission tomography, dynamic contrast‐enhanced and diffusion‐weighted MRI
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Cediranib is a small‐molecule pan‐vascular endothelial growth factor receptor inhibitor. The tumor response to short‐term cediranib treatment was studied using dynamic contrast‐enhanced and diffusion‐weighted MRI at 7 T, as well as 18F‐fluoromisonidazole positron emission tomography and histological markers. Rats bearing subcutaneous HT29 human colorectal tumors were imaged at baseline; they then received three doses of cediranib (3 mg/kg per dose daily) or vehicle (dosed daily), with follow‐up imaging performed 2 h after the final cediranib or vehicle dose. Tumors were excised and evaluated for the perfusion marker Hoechst 33342, the endothelial cell marker CD31, smooth muscle actin, intercapillary distance and tumor necrosis. Dynamic contrast‐enhanced MRI‐derived ...
Lactate detection in inducible and orthotopic Her2/neu mammary gland tumours in mouse models
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This study compared the steady state concentration of lactate in an inducible Her2/nue transgenic breast cancer mouse model and in tumours from the same Her2/neu model grown orthotopically. In vivo lactate was detected by MRS using the Hadamard encoded selective multiple quantum coherence pulse sequence (HadSelMQC) recently developed by our laboratory. A lower lactate signal was observed in the inducible tumours compared to orthotopic tumours in vivo, while ex vivo analysis of perchloric acid extracts revealed similar amounts of this metabolite in both models. Histological staining of mammary tumour specimens showed a much higher level of fat tissue in inducible tumours compared to the orthotopic model. Phantom studies with [3‐13C] lactate indicated that a lipid environment could signifi...
31P and 1H MRS of DB‐1 melanoma xenografts: lonidamine selectively decreases tumor intracellular pH and energy status and sensitizes tumors to melphalan
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In vivo31P MRS demonstrates that human melanoma xenografts in immunosuppressed mice treated with lonidamine (LND, 100 mg/kg intraperitoneally) exhibit a decrease in intracellular pH (pHi) from 6.90 ± 0.05 to 6.33 ± 0.10 (p < 0.001), a slight decrease in extracellular pH (pHe) from 7.00 ± 0.04 to 6.80 ± 0.07 (p > 0.05) and a monotonic decline in bioenergetics (nucleoside triphosphate/inorganic phosphate) of 66.8 ± 5.7% (p < 0.001) relative to the baseline level. Both bioenergetics and pHi decreases were sustained for at least 3 h following LND treatment. Liver exhibited a transient intracellular acidification by 0.2 ± 0.1 pH units (p > 0.05) at 20 min post‐LND, with no significant change in pHe and a small transient decrease ...
MRI assessment of the intra‐carotid route for macrophage delivery after transient cerebral ischemia
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The broad aim underlying the present research was to investigate the distribution and homing of bone marrow‐derived macrophages in a rodent model of transient middle cerebral artery occlusion using MRI and ultrasmall superparamagnetic iron oxide (USPIO) to magnetically label bone marrow‐derived macrophages. The specific aim was to assess the intra‐carotid infusion route for bone marrow‐derived macrophage delivery at reperfusion. Fifteen Sprague–Dawley rats sustained 1 h of middle cerebral artery occlusion. USPIO‐labeled bone marrow‐derived macrophages were slowly injected for 5 min immediately after reperfusion in ischemic animals (n = 7), 1 h after the end of surgery in sham animals (n = 5) and very shortly after anesthesia in healthy animals (n = 3). Multiparame...
Detection of endogenous iron deposits in the injured mouse spinal cord through high‐resolution ex vivo and in vivo MRI
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The main aim of this study was to employ high‐resolution MRI to investigate the spatiotemporal development of pathological features associated with contusive spinal cord injury (SCI) in mice. Experimental mice were subjected to either sham surgery or moderate contusive SCI. A 16.4‐T small‐animal MR system was employed for nondestructive imaging of post‐mortem, fixed spinal cord specimens at the subacute (7 days) and more chronic (28–35 days) stages post‐injury. Routine histological techniques were used for subsequent investigation of the observed neuropathology at the microscopic level. The central core of the lesion appeared as a dark hypo‐intense area on MR images at all time points investigated. Small focal hypo‐intense spots were also observed spreading through the ...
Doubly selective multiple quantum chemical shift imaging and T1 relaxation time measurement of glutathione (GSH) in the human brain in vivo
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Mapping of a major antioxidant, glutathione (GSH), was achieved in the human brain in vivo using a doubly‐selective multiple quantum filtering based chemical shift imaging (CSI) of GSH at 3 T. Both in vivo and phantom tests in CSI and single voxel measurements were consistent with excellent suppression of overlapping signals from creatine, γ‐Amino butyric acid (GABA) and macromolecules. GSH concentration in the fronto‐parietal region was 1.20 ± 0.16 µmol/g (mean ± SD, n = 7). The longitudinal relaxation time (T1) of GSH in the human brain was 397 ± 44 ms (mean ± SD, n = 5), which was substantially shorter than that of other metabolites. This GSH‐CSI method permits us to address regional differences of GSH in the human brain under conditions where...
The role of gray and white matter segmentation in quantitative proton MR spectroscopic imaging
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Since the brain's gray matter (GM) and white matter (WM) metabolite concentrations differ, their partial volumes can vary the voxel's 1H MR spectroscopy (1H‐MRS) signal, reducing sensitivity to changes. While single‐voxel 1H‐MRS cannot differentiate between WM and GM signals, partial volume correction is feasible by MR spectroscopic imaging (MRSI) using segmentation of the MRI acquired for VOI placement. To determine the magnitude of this effect on metabolic quantification, we segmented a 1‐mm3 resolution MRI into GM, WM and CSF masks that were co‐registered with the MRSI grid to yield their partial volumes in approximately every 1 cm3 spectroscopic voxel. Each voxel then provided one equation with two unknowns: its i‐ metabolite's GM and WM concentrations CiGM, CiWM. With the ...
Noninvasive quantification of intracellular sodium in human brain using ultrahigh–field MRI
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In this study, we report the first noninvasive quantitative in vivo measurement of ISC and intracellular sodium volume fraction (ISVF) in healthy human brain, made possible by measuring tissue sodium concentration (TSC) and intracellular sodium molar fraction (ISMF) at ultra‐high field MRI. The method uses single–quantum (SQ) and triple–quantum filtered (TQF) imaging at 7 Tesla to separate intra‐ and extracellular sodium signals and provide quantification of ISMF, ISC and ISVF. This novel method allows noninvasive quantitative measurement of ISC and ISVF, opening many possibilities for structural and functional metabolic studies in healthy and diseased brains. Copyright © 2012 John Wiley & Sons, Ltd.In this study, we report a non‐invasive quantitative in vivo measurement of ...
Quantification issues of in vivo 1H NMR spectroscopy of the rat brain investigated at 16.4 T
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The accuracy and precision of the quantification of metabolite concentrations in in vivo 1H NMR spectroscopy are affected by linewidth and signal‐to‐noise ratio (SNR). To study the effect of both factors in in vivo 1H NMR spectra acquired at ultrahigh field, a reference spectrum was generated by summing nine in vivo 1H NMR spectra obtained in rat brain with a STEAM sequence at 16.4 T. By progressive deterioration of linewidth and SNR, 6400 single spectra were generated. In an accuracy study, the variation in the mean concentrations of five metabolites was mainly dependent on SNR, whereas 11 metabolites were predominantly susceptible to the linewidth. However, the standard deviations of the concentrations obtained were dependent almost exclusively on the SNR. An insignificant correlat...
Quantification issues of in vivo1H NMR spectroscopy of the rat brain investigated at 16.4 T
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The accuracy and precision of the quantification of metabolite concentrations in in vivo1H NMR spectroscopy are affected by linewidth and signal‐to‐noise ratio (SNR). To study the effect of both factors in in vivo1H NMR spectra acquired at ultrahigh field, a reference spectrum was generated by summing nine in vivo1H NMR spectra obtained in rat brain with a STEAM sequence at 16.4 T. By progressive deterioration of linewidth and SNR, 6400 single spectra were generated. In an accuracy study, the variation in the mean concentrations of five metabolites was mainly dependent on SNR, whereas 11 metabolites were predominantly susceptible to the linewidth. However, the standard deviations of the concentrations obtained were dependent almost exclusively on the SNR. An insignificant correlation...
NMR studies of preimplantation embryo metabolism in human assisted reproductive techniques: a new biomarker for assessment of embryo implantation potential
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There has been growing interest in understanding energy metabolism in human embryos generated using assisted reproductive techniques (ART) for improving the overall success rate of the method. Using NMR spectroscopy as a noninvasive tool, we studied human embryo metabolism to identify specific biomarkers to assess the quality of embryos for their implantation potential. The study was based on estimation of pyruvate, lactate and alanine levels in the growth medium, ISM1, used in the culture of embryos. An NMR study involving 127 embryos from 48 couples revealed that embryos transferred on Day 3 (after 72 h in vitro culture) with successful implantation (pregnancy) exhibited significantly (p < 10‐5) lower pyruvate/alanine ratios compared to those that failed to implant. Lactate le...
Decreased lactate concentration and glycolytic enzyme expression reflect inhibition of mTOR signal transduction pathway in B‐cell lymphoma
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The application of kinase inhibitors in cancer treatment is growing rapidly. However, methods for monitoring the effectiveness of the inhibitors are still poorly developed and currently rely mainly on the tracking of changes in the tumor volume, a rather late and relatively insensitive marker of the therapeutic response. In contrast, MRS can detect changes in cell metabolism and has the potential to provide early and patient‐specific markers of drug activity. Using human B‐cell lymphoma models and MRS, we have demonstrated that the inhibition of the mTOR signaling pathway can be detected in malignant cells in vitro and noninvasively in vivo by the measurement of lactate levels. An mTOR inhibitor, rapamycin, suppressed lactic acid production in lymphoma cell line cultures and also dimin...
An in vivo ultrahigh field 14.1 T 1H‐MRS study on 6‐OHDA and α‐synuclein‐based rat models of Parkinson's disease: GABA as an early disease marker
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This study aimed at using MRS on an ultrahigh field 14.1 T magnet to explore the striatal metabolic changes occurring in two different rat models of the disease. Rats lesioned by the injection of 6‐hydroxydopamine (6‐OHDA) in the medial‐forebrain bundle were used to model a complete nigrostriatal lesion while a genetic model based on the nigral injection of an adeno‐associated viral (AAV) vector coding for the human α‐synuclein was used to model a progressive neurodegeneration and dopaminergic neuron dysfunction, thereby replicating conditions closer to early pathological stages of PD. MRS measurements in the striatum of the 6‐OHDA rats revealed significant decreases in glutamate and N‐acetyl‐aspartate levels and a significant increase in GABA level in the ipsilateral he...
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No abstract is available for this article. (Source: NMR in Biomedicine)
Feasibility of noninvasive quantitative measurements of intrarenal R2′ in humans using an asymmetric spin echo echo planar imaging sequence
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The purpose of this study was to demonstrate the feasibility of an asymmetric spin echo (ASE) single‐shot echo planar imaging (EPI) sequence for the noninvasive quantitative measurement of intrarenal R2′ in humans within 20 s. The reproducibility of R2′ measurements with the ASE‐EPI sequence was assessed in nine healthy young subjects in repeated studies conducted over three consecutive days. Moreover, we also evaluated whether the ASE‐EPI sequence‐measured R2′ reflected the intrarenal oxygenation changes induced by furosemide in another group of normal human subjects (n = 10). Different flow attenuation gradients (b = 0, 40 and 80 s/mm2) were utilized to examine the impact of the intravascular signal contribution on the estimation of intrarenal R2′. In the abse...
Feasibility of measuring prostate perfusion with arterial spin labeling
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Prostate perfusion has the potential to become an important pathophysiological marker for the monitoring of disease progression or the assessment of the therapeutic response of prostate cancer. The feasibility of arterial spin labeling, an MRI approach for the measurement of perfusion without an exogenous contrast agent, is demonstrated in the prostate for the first time. Although various arterial spin labeling methods have been demonstrated previously in highly perfused organs, such as the brain and kidneys, the prospect of obtaining such measurements in the prostate is challenging because of the relatively low blood flow, long transit times, susceptibility‐induced image distortion and local motion. However, despite these challenges, this study demonstrates that, with a whole‐body tra...
Pushing the limits of high‐resolution functional MRI using a simple high‐density multi‐element coil design
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Recent studies have shown that functional MRI (fMRI) can be sensitive to the laminar and columnar organization of the cortex based on differences in the spatial and temporal characteristics of the blood oxygenation level‐dependent (BOLD) signal originating from the macrovasculature and the neuronal‐specific microvasculature. Human fMRI studies at this scale of the cortical architecture, however, are very rare because the high spatial/temporal resolution required to explore these properties of the BOLD signal are limited by the signal‐to‐noise ratio. Here, we show that it is possible to detect BOLD signal changes at an isotropic spatial resolution as high as 0.55 mm at 7 T using a high‐density multi‐element surface coil with minimal electronics, which allows close proximity to t...
Structural and functional abnormalities in migraine patients without aura
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Migraine is a primary headache disorder characterized by recurrent attacks of throbbing pain associated with neurological, gastrointestinal and autonomic symptoms. Previous studies have detected structural deficits and functional impairments in migraine patients. However, researchers have failed to investigate the functional connectivity alterations of regions with structural deficits during the resting state. Twenty‐one migraine patients without aura and 21 age‐ and gender‐matched healthy controls participated in our study. Voxel‐based morphometric (VBM) analysis and functional connectivity were employed to investigate the abnormal structural and resting‐state properties, respectively, in migraine patients without aura. Relative to healthy comparison subjects, migraine patients ...
Feasibility of measurement of prostate perfusion with arterial spin labeling
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Prostate perfusion has the potential to become an important pathophysiological marker for the monitoring of disease progression or the assessment of the therapeutic response of prostate cancer. The feasibility of arterial spin labeling, an MRI approach for the measurement of perfusion without an exogenous contrast agent, is demonstrated in the prostate for the first time. Although various arterial spin labeling methods have been demonstrated previously in highly perfused organs, such as the brain and kidneys, the prospect of obtaining such measurements in the prostate is challenging because of the relatively low blood flow, long transit times, susceptibility‐induced image distortion and local motion. However, despite these challenges, this study demonstrates that, with a whole‐body tra...
Multiexponential T2 analyses in a murine model of hepatic fibrosis at 11.7 T MRI
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This study evaluated the effects of hepatic fibrosis on the multiexponential T2 (MET2) relaxation of ex vivo murine liver specimens using an 11.7 T MRI. This animal study was approved by the Institutional Animal Care and Use Committee. Eighteen male C57BL/6 mice were divided into control (n = 3) and experimental (n = 15) groups; the latter group was fed a 3,5‐dicarbethoxy‐1,4‐dihydrocollidine‐supplemented diet to induce hepatic fibrosis. Ex vivo liver specimens were imaged using an 11.7 T MRI scanner. A multi‐echo spin‐echo sequence was utilized for subsequent MET2 analysis. Degrees of fibrosis were determined by a pathologist, as well as by digital image analysis. Scatterplot graphs comparing various features of the MET2 signal decay with the degrees of fibrosis were g...
Diffusion abnormalities in temporal lobes of children with temporal lobe epilepsy: a preliminary diffusional kurtosis imaging study and comparison with diffusion tensor imaging
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In this preliminary study, we aimed to investigate the abnormalities of water diffusion in children with temporal lobe epilepsy (TLE). Eight children with unilateral TLE (according to electroencephalography, EEG) and eight age‐ and sex‐matched controls were recruited. Diffusion tensor imaging (DTI)/diffusional kurtosis imaging (DKI) acquisitions were performed. Radial diffusivity (λ⊥), axial diffusivity (λ∥), mean diffusivity (MD) and fractional anisotropy (FA) maps were calculated for both DTI and DKI, and radial kurtosis (K⊥), axial kurtosis (K∥) and mean kurtosis (MK) maps were calculated for DKI only. Mann–Whitney test showed that, for white matter in the temporal lobe, DKI‐derived λ∥, MD and K∥ were significantly different in bilateral temporal lobes and EEG‐a...
Oxygenation in cervical cancer and normal uterine cervix assessed using blood oxygenation level‐dependent (BOLD) MRI at 3T
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This study examined the potential use of blood oxygenation level‐dependent (BOLD) contrast MRI as a noninvasive technique to assess tumor vascular oxygenation at 3T. Following Institutional Review Board‐approved informed consent and in compliance with the Health Insurance Portability and Accountability Act, successful results were achieved in nine patients with locally advanced cervical cancer [International Federation of Gynecology and Obstetrics (FIGO) stage IIA to IVA] and three normal volunteers. In the first four patients, dynamic T2*‐weighted MRI was performed in the transaxial plane using a multi‐shot echo planar imaging sequence whilst patients breathed room air followed by oxygen (15 dm3/min). Later, a multi‐echo gradient echo examination was added to provide quantitativ...