NMR in Biomedicine

Cover image for Vol. 24 Issue 10

December 2011

Volume 24, Issue 10

Pages 1181–1432

  1. Rapid Communications

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    2. Rapid Communications
    3. Research Articles
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    5. Research Articles
    1. Diffusion-weighted MRI in early chemotherapy response evaluation of patients with diffuse large B-cell lymphoma – a pilot study: comparison with 2-deoxy-2-fluoro- D-glucose-positron emission tomography/computed tomography (pages 1181–1190)

      Xingchen Wu, Pirkko-Liisa Kellokumpu-Lehtinen, Hannu Pertovaara, Pasi Korkola, Seppo Soimakallio, Hannu Eskola and Prasun Dastidar

      Version of Record online: 8 MAR 2011 | DOI: 10.1002/nbm.1689

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      Eight patients with aggressive non-Hodgkin's lymphoma were imaged by MRI, including diffusion-weighted imaging, and positron emission tomography/computed tomography (PET/CT) before treatment (E1), and after 1 week (E2) and two cycles (E3) of chemotherapy. The mean pre-therapy apparent diffusion coefficient (ADC) was 0.71 × 10–3 mm2/s; it increased by 77% at E2 (p<0.05) and 24% more at E3. The results of DWI in combination with whole-body MRI were found to be comparable with those of integrated PET/CT.

  2. Research Articles

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    5. Research Articles
    1. Spatiotemporal encoding as a robust basis for fast three-dimensional in vivo MRI (pages 1191–1201)

      Noam Ben-Eliezer and Lucio Frydman

      Version of Record online: 28 FEB 2011 | DOI: 10.1002/nbm.1673

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      New approaches to the fast imaging of three-dimensional (3D) objects are evaluated based on the use of spatiotemporal encoding concepts. When these approaches (a) were compared against conventional echo planar imaging (EPI)-based MRI sequences (b), they systematically afforded results that more faithfully reproduced the 3D MR images arising from fast low-angle shot (FLASH) protocols (c). The reasons underlying this improved performance are discussed, and a number of different versions and potential uses of these new sequences are presented.

    2. B0 field inhomogeneity considerations in pseudo-continuous arterial spin labeling (pCASL): effects on tagging efficiency and correction strategy (pages 1202–1209)

      Hesamoddin Jahanian, Douglas C. Noll and Luis Hernandez-Garcia

      Version of Record online: 8 MAR 2011 | DOI: 10.1002/nbm.1675

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      In this study, we reported our findings on the effect of B0 field inhomogeneity on the tagging efficiency of the pseudo-continuous arterial spin labeling (pCASL) pulse sequence. We showed our theoretical framework for this problem and verified it on simulated and in vivo data. We also proposed a method utilizing B0 field map information to correct for the possible loss in tagging efficiency of pCASL and allow for a more robust use of pCASL in clinical and research applications.

    3. Gadolinium diethylenetriaminepentaacetate enhancement kinetics in the menisci of asymptomatic subjects: a first step towards a dedicated dGEMRIC (delayed gadolinium-enhanced MRI of cartilage)-like protocol for biochemical imaging of the menisci (pages 1210–1215)

      Marius E. Mayerhoefer, Tallal C. Mamisch, Georg Riegler, Goetz H. Welsch, Tomas Dobrocky, Michael Weber, Sebastian Apprich, Georg Scheurecker, Pavol Szomolanyi, Stefan Puchner and Siegfried Trattnig

      Version of Record online: 24 MAR 2011 | DOI: 10.1002/nbm.1676

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      The maximum enhancement in the menisci of asymptomatic subjects occured approximately 2.5 h after intravenous gadolinium diethylenetriaminepentaacetate (Gd-DTPA2−) administration, and thus considerably later than reported for articular cartilage. In the menisci, no equilibrium enhancement phase, but an enhancement peak that lasted from approximately 2.5 to 4.5 h after contrast medium (CM) application, was observed.

    4. A lanthanide complex with dual biosensing properties: CEST (chemical exchange saturation transfer) and BIRDS (biosensor imaging of redundant deviation in shifts) with europium DOTA–tetraglycinate (pages 1216–1225)

      Daniel Coman, Garry E. Kiefer, Douglas L. Rothman, A. Dean Sherry and Fahmeed Hyder

      Version of Record online: 15 MAR 2011 | DOI: 10.1002/nbm.1677

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      A variety of LnDOTA–tetraamide complexes have been demonstrated as responsive contrast agents (RCAs) for molecular imaging with chemical exchange saturation transfer (CEST). Molecular imaging is also possible when RCA itself is observed, using biosensor imaging of redundant deviation in shifts (BIRDS). The in vitro temperature sensitivity of EuDOTA- (gly)4 is used to show that qualitative MR contrast with CEST can be calibrated using quantitative MR mapping with BIRDS, thereby enabling quantitative molecular imaging at high spatial resolution.

    5. Hexamethyldisiloxane-based nanoprobes for 1H MRI oximetry (pages 1226–1234)

      Praveen K. Gulaka, Ujjawal Rastogi, Madalyn A. McKay, Xianghui Wang, Ralph P. Mason and Vikram D. Kodibagkar

      Version of Record online: 15 MAR 2011 | DOI: 10.1002/nbm.1678

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      This study presents the first pO2 nanoprobes for quantitative 1H MRI oximetry. Hexamethyldisiloxane (HMDSO)-based nanoemulsions were synthesized using biocompatible, polyethylene glycolated emulsifiers and characterized with respect to particle size and sensitivity to pO2 changes. Optimal nanoprobes were identified and used in vivoin conjunction with the PISTOL (proton imaging of siloxanes to map tissue oxygenation levels) technique for 1H MRI oximetry to assess dynamic changes in mean thigh tissue pO2, and oxygen consumption and washout kinetics.

    6. In vivo and ex vivo evidence for ketamine-induced hyperglutamatergic activity in the cerebral cortex of the rat: Potential relevance to schizophrenia (pages 1235–1242)

      Sang-Young Kim, Hyunseung Lee, Hyun-Ju Kim, Eunjung Bang, Sung-Ho Lee, Do-Wan Lee, Dong-Cheol Woo, Chi-Bong Choi, Kwan Soo Hong, Chulhyun Lee and Bo-Young Choe

      Version of Record online: 11 MAY 2011 | DOI: 10.1002/nbm.1681

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      The present study demonstrated that administration of a subanesthetic dose of ketamine had a significant effect on glutamate (Glu) neurotransmission in the cerebral cortex of rats using in vivo 1H-MRS and ex vivo 1H high-resolution magic angle spinning (HR-MAS) spectroscopy. Repeated administration of ketamine increased glutamate concentrations in the cerebral cortex of the rat compared with saline-treated group. Our results suggest that a subanesthetic dose of ketamine administration in the rat may exert at least part of their effect in the cerebral cortex by activation of glutamatergic neurotransmission.

    7. 13C High-resolution-magic angle spinning MRS reveals differences in glucose metabolism between two breast cancer xenograft models with different gene expression patterns (pages 1243–1252)

      Maria T. Grinde, Siver A. Moestue, Eldrid Borgan, Øystein Risa, Olav Engebraaten and Ingrid S. Gribbestad

      Version of Record online: 4 APR 2011 | DOI: 10.1002/nbm.1683

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      13C high-resolution-magic angle spinning (HR-MAS) MRS and gene expression analysis were performed to study the glycolytic activity in two breast cancer xenograft models representing basal-like and luminal-like genetic profiles. 13C HR-MAS MRS was performed both on untreated mice and a group of mice that received an injection of [1-13C]-glucose 10 or 15min before harvesting the tissue. The lower glucose/alanine and glucose/lacate ratios and higher glycolytic gene expression observed in the luminal-like model indicated that transformation of glucose to lactate and alanine occurred faster in this model than in the basal-like model, which has a growth rate several times faster than that of the luminal-like model.

    8. Regional determination of oxygen uptake in rodent lungs using hyperpolarized gas and an analytical treatment of intrapulmonary gas redistribution (pages 1253–1263)

      Stephen Kadlecek, Puttisarn Mongkolwisetwara, Yi Xin, Masaru Ishii, Harilla Profka, Kiarash Emami and Rahim Rizi

      Version of Record online: 8 MAR 2011 | DOI: 10.1002/nbm.1685

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      An MRI-based method is presented for the measurement of alveolar oxygen levels and uptake in small-animal lungs. Quantitative treatment of gas flow within the lung is found to be necessary for accurate extraction of the oxygen uptake rate, and may itself be an informative measure of the disease state.

    9. Hyperpolarized 129Xe NMR signature of living biological cells (pages 1264–1269)

      Céline Boutin, Hervé Desvaux, Marie Carrière, François Leteurtre, Nadège Jamin, Yves Boulard and Patrick Berthault

      Version of Record online: 15 MAR 2011 | DOI: 10.1002/nbm.1686

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      Hyperpolarized xenon-129 introduced in a solution of biological cells suspended in their culture medium acts as a tracer. Indeed its NMR spectrum reveals a signal specific of the cytoplasm compartment. The presence of such a signal obtained in a very short time provides valuable information: it is indicative of the integrity of the cells and can lead to applications such as study of the membrane fluidity.

    10. 1H MRS of basal ganglia and thalamus in amyotrophic lateral sclerosis (pages 1270–1276)

      Khema R. Sharma, Gaurav Saigal, Andrew A. Maudsley and Varan Govind

      Version of Record online: 15 MAR 2011 | DOI: 10.1002/nbm.1687

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      The 1H MRS-observable brain metabolites N-acetylaspartate (NAA), choline (Cho) and their ratio (NAA/Cho) were evaluated in the basal ganglia (lentiform nuclei and caudate) and thalamus of 14 patients with amyotrophic lateral sclerosis (ALS) and in 17 age-matched controls at 3T. In patients, the metabolites and their ratio were significantly different from controls in these structures, except for Cho and NAA/Cho in the caudate. The observed changes indicate neuronal loss or dysfunction in these structures in patients with ALS.

    11. Efficient γ-aminobutyric acid editing at 3T without macromolecule contamination: MEGA-SPECIAL (pages 1277–1285)

      Jamie Near, Robin Simpson, Philip Cowen and Peter Jezzard

      Version of Record online: 8 MAR 2011 | DOI: 10.1002/nbm.1688

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      A new method is presented for in vivo MRS measurement of γ-aminobutyric acid (GABA) levels in the human brain. This method enables the removal of unwanted macromolecule contamination and provides improved GABA editing efficiency compared with conventional GABA MRS. Successful application of this technique is demonstrated in vivo using standard hardware on a clinical 3-T MRI system.

    12. Improved specificity of cartilage matrix evaluation using multiexponential transverse relaxation analysis applied to pathomimetically degraded cartilage (pages 1286–1294)

      David A. Reiter, Remigio A. Roque, Ping-Chang Lin, Stephen B. Doty, Nancy Pleshko and Richard G. Spencer

      Version of Record online: 5 APR 2011 | DOI: 10.1002/nbm.1690

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      We sought to improve the specificity of cartilage matrix evaluation through multiexponential analysis of T2 relaxation, which can delineate macromolecular compartments with different water fraction and mobilies. Multiexponential T2 analysis of control cartilage and of cartilage subjected to two enzymatic degradation protocols showed distinct patterns, consistent with the known actions of the degradative enzymes used. Multiexponential T2 analysis demonstrates greatly improved specificity over standard monoexponential T2 analysis to changes in cartilage matrix, indicating its diagnostic potential for the detection of cartilage disease.

    13. Longitudinal evaluation of intramyocellular lipids (IMCLs) in tibialis anterior muscle of ob/ob and ob/+ control mice using a cryogenic surface coil at 9.4 T (pages 1295–1301)

      Qiong Ye, Carsten Friedrich Danzer, Alexander Fuchs, Wilhelm Krek, Thomas Mueggler, Christof Baltes and Markus Rudin

      Version of Record online: 24 MAR 2011 | DOI: 10.1002/nbm.1691

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      Intramyocellular lipid (IMCL) levels were found to be significantly higher in ob/ob mice relative to ob/+ heterozygous control mice that do not develop disease. This increase in IMCL levels was observed until weeks 16/17; after this time point, IMCL levels started to decrease again, reaching final levels that were slightly higher than the initial values. These noninvasively detected alterations in skeletal muscle lipid metabolism in ob/ob mice were accompanied by elevated plasma insulin concentrations.

    14. You have full text access to this OnlineOpen article
      A brain MRI study of chronic fatigue syndrome: evidence of brainstem dysfunction and altered homeostasis (pages 1302–1312)

      Leighton R. Barnden, Benjamin Crouch, Richard Kwiatek, Richard Burnet, Anacleto Mernone, Steve Chryssidis, Garry Scroop and Peter Del Fante

      Version of Record online: 11 MAY 2011 | DOI: 10.1002/nbm.1692

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      Voxel-wise regressions of MRI levels versus clinical scores in chronic fatigue syndrome (CFS) suggested volume loss in the midbrain, and altered homeostasis in the brain stem, prefrontal white matter and the hypothalamus. The effect of an insult to the midbrain at onset may persist and disrupt multiple feedback loops.

    15. Measurement of absolute arterial cerebral blood volume in human brain without using a contrast agent (pages 1313–1325)

      Jun Hua, Qin Qin, James J. Pekar and Peter C. M. van Zijl

      Version of Record online: 24 MAY 2011 | DOI: 10.1002/nbm.1693

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      We extended the recently developed inflow vascular-space-occupancy (iVASO) MRI technique to quantify absolute arterial/arteriolar CBV (CBVa) and arterial transit time without exogenous contrast agent administration. Human brain gray matter CBVa values were 2.04 ± 0.27 and 0.76 ± 0.17 mL blood/100 mL tissue without and with applying velocity-dependent bipolar crusher gradients, respectively. Arterial transit times were 671 ± 43 and 785 ± 69 ms, respectively. The arterial origin of the signal was validated by measuring its T2 relaxation time.

    16. Detection of neuronal activity and metabolism in a model of dehydration-induced anorexia in rats at 14.1 T using manganese-enhanced MRI and 1H MRS (pages 1326–1336)

      Nathalie Just and Rolf Gruetter

      Version of Record online: 4 MAY 2011 | DOI: 10.1002/nbm.1694

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      At 24 h after intravenous injection of MnCl2, three-dimensional, gradient echo, MR images acquired at 14.1 T showed increased enhancement of the paraventricular nuclei and the lateral hypothalamus in female rats submitted to dehydration-induced anorexia (DIA) by drinking hypertonic saline compared with control rats (CTL) and rats subjected to overnight food suppression (OFS). 1H MRS in a voxel encompassing the paraventricular nuclei of the hypothalamus of DIA rats demonstrated a significant increase in γ-aminobutyric acid (GABA), an important inhibitory neurotransmitter of the hypothalamus.

    17. 31P MRSI and 1H MRS at 7 T: initial results in human breast cancer (pages 1337–1342)

      Dennis W. J. Klomp, Bart L. van de Bank, Alexander Raaijmakers, Mies A. Korteweg, Cecilia Possanzini, Vincent O. Boer, Cornelius A. T. van de Berg, Maurice A. A. J. van de Bosch and Peter R. Luijten

      Version of Record online: 24 MAR 2011 | DOI: 10.1002/nbm.1696

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      1H MR images and spectra and 31P MRS images were acquired from a patient on neoadjuvant chemotherapy treatment. Modulation in total choline and tumor volume was observed, and alterations in phospholipid metabolite levels [phosphoethanolamine (PE), glycerol phosphocholine (GPC), glycerol phosphoethanolamine (GPE)] and inorganic phosphate (Pi) were detected in 10-mL volumes at 7 T.

    18. Hyperpolarized 129Xe lung MRI in spontaneously breathing mice with respiratory gated fast imaging and its application to pulmonary functional imaging (pages 1343–1352)

      Hirohiko Imai, Atsuomi Kimura, Yuki Hori, Satoshi Iguchi, Takuya Kitao, Emi Okubo, Tsuyoshi Ito, Toshio Matsuzaki and Hideaki Fujiwara

      Version of Record online: 2 MAY 2011 | DOI: 10.1002/nbm.1697

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      Fast imaging techniques of the balanced steady-state free precession (bSSFP) sequence combined with compressed sensing (CS) and respiratory gating were applied to hyperpolarized 129Xe lung imaging in spontaneously breathing mice. These protocols allowed the mapping of pulmonary functions and made it possible to extract abnormal ventilation and gas exchange simultaneously in elastase-induced mouse models of emphysema.

  3. Research Articless

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    3. Research Articles
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    5. Research Articles
    1. Longitudinal study of tumor-associated macrophages during tumor expansion using MRI (pages 1353–1360)

      Yen-Yu I. Shih, Yi-Hua Hsu, Timothy Q. Duong, Sui-Shan Lin, Kai-Ping N. Chow and Chen Chang

      Version of Record online: 24 MAR 2011 | DOI: 10.1002/nbm.1698

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      With a single bolus injection of iron oxide contrast agent, tumor-associated macrophages (TAMs) can be tracked in vivo during tumorigenesis. The hypointense areas induced by iron oxide-labeled TAMs served as an anchor point for subsequent tumor expansion. Our findings may benefit the future study of TAM behavior in tumors and the development of macrophage-targeted therapies.

  4. Research Articles

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    1. In vivo MR tracking of therapeutic microglia to a human glioma model (pages 1361–1368)

      Emeline J. Ribot, Sylvain Miraux, Jan P. Konsman, Véronique Bouchaud, Line Pourtau, Marie-Hélène Delville, Jean-Michel Franconi, Eric Thiaudière and Pierre J. Voisin

      Version of Record online: 8 MAR 2011 | DOI: 10.1002/nbm.1699

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      Microglia can be used as a therapeutic vehicle to transport the thymidine kinase gene and gadolinium-based silica nanoparticles into brain tumors. In vivo MRI shows that, as soon as 24 h after systemic injection, contrast agent-labeled microglia are efficiently chemoattracted to human glioma implanted in the brains of nude mice. Systemic injection of a thymidine kinase substrate induces a significantly prolonged survival time of the mice.

    2. High-resolution diffusion tensor imaging of fixed brain in a mouse model of Pelizaeus–Merzbacher disease: comparison with quantitative measures of white matter pathology (pages 1369–1379)

      Torsten Ruest, William M. Holmes, Jennifer A. Barrie, Ian R. Griffiths, Thomas J. Anderson, Deborah Dewar and Julia M. Edgar

      Version of Record online: 24 MAR 2011 | DOI: 10.1002/nbm.1700

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      High-resolution ex vivo diffusion tensor imaging was combined with quantitative histology to characterise brain white matter pathology in a mouse model of the leucodystrophy Pelizaeus–Merzbacher disease. There were widespread changes throughout the brain of Plp1-transgenic mice in axial (λ1) and radial (RD) diffusivities and fractional anisotropy (FA). Regions with increased λ1 and RD and decreased FA exhibited an almost complete absence of myelin, preserved axons, marked astrocytosis and increased or unchanged glial cell densities.

    3. Imaging the extracellular pH of tumors by MRI after injection of a single cocktail of T1 and T2 contrast agents (pages 1380–1391)

      Gary V. Martinez, Xiaomeng Zhang, María L. García-Martín, David L. Morse, Mark Woods, A. Dean Sherry and Robert J. Gillies

      Version of Record online: 23 MAY 2011 | DOI: 10.1002/nbm.1701

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      A single-infusion protocol consisting of the slow infusion of a contrast agent cocktail yielded high-resolution extracellular pH (pHe) maps of tumors. The current method is based on a calibration between [Gd] derived from T1-weighted spin echo and ΔR2*. The primary advantage of this protocol over previous studies is the rapidity of generating the pHe measurement after the calibration curve has been obtained.

    4. The differences in neural network activity between methamphetamine abusers and healthy subjects performing an emotion-matching task: functional MRI study (pages 1392–1400)

      Yang-Tae Kim, Hui-Jin Song, Jee-Hye Seo, Jae-Jun Lee, Jongmin Lee, Do-Hoon Kwon, Done-Sik Yoo, Hui Joong Lee, Kyung-Jin Suh and Yongmin Chang

      Version of Record online: 7 APR 2011 | DOI: 10.1002/nbm.1702

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    5. Rat strain-dependent variations in brain metabolites detected by in vivo 1H NMR spectroscopy at 16.4T (pages 1401–1407)

      Sung-Tak Hong, David Z. Balla, Changho Choi and Rolf Pohmann

      Version of Record online: 4 APR 2011 | DOI: 10.1002/nbm.1703

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      Interstrain differences in metabolite concentrations were investigated in two brain regions of three commonly used strains, which resulted in moderate but significant interstrain variations, depending on the brain region. Twenty metabolites could be quantified in all brain regions and rat strains, confirming the high quality of the neurochemical profile acquired at a field strength of 16.4 T.

    6. MRS characterization of central neurocytomas using glycine (pages 1408–1413)

      Tariq Shah, Rama Jayasundar, Virendera Paul Singh and Chitra Sarkar

      Version of Record online: 4 APR 2011 | DOI: 10.1002/nbm.1705

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      The presence of glycine in the 1H MR spectrum is a characteristic feature of central neurocytomas and can be used to characterize and differentiate them from other tumors.

    7. Correlation between the temperature dependence of intrinsic MR parameters and thermal dose measured by a rapid chemical shift imaging technique (pages 1414–1421)

      B. A. Taylor, A. M. Elliott, K. P. Hwang, J. D. Hazle and R. J. Stafford

      Version of Record online: 1 JUL 2011 | DOI: 10.1002/nbm.1707

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      Temperature-dependent changes in the proton resonance frequency, R2*, and T1-W amplitudes were measured simultaneously in ex vivo tissue heated with a 980-nm laser at 1.5T and 3.0T. Changes in the temperature sensitivity of R2* and, in some instances, T1-W amplitudes were found to be correlated with damage predicted by an Arrhenius dose rate model.

    8. Towards compartment size estimation in vivo based on double wave vector diffusion weighting (pages 1422–1432)

      Martin A. Koch and Jürgen Finsterbusch

      Version of Record online: 14 JUL 2011 | DOI: 10.1002/nbm.1711

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      In restricted diffusion, the MR signal with two successive diffusion weighting periods depends on the relative gradient orientation. The signal difference between parallel and antiparallel gradient orientation scales with the pore size. This is used in vivo in the human corticospinal tract to derive an estimate of compartment or pore size.

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