NMR in Biomedicine

Cover image for Vol. 26 Issue 12

December 2013

Volume 26, Issue 12

Pages i–ii, 1609–1886

  1. Issue information

    1. Top of page
    2. Issue information
    3. Review articles
    4. Research articles
    1. Issue Information (pages i–ii)

      Article first published online: 20 NOV 2013 | DOI: 10.1002/nbm.2865

  2. Review articles

    1. Top of page
    2. Issue information
    3. Review articles
    4. Research articles
    1. Quantitative proton MR techniques for measuring fat (pages 1609–1629)

      H. H. Hu and H. E. Kan

      Article first published online: 3 OCT 2013 | DOI: 10.1002/nbm.3025

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      Proton MR provides several techniques for body fat quantification, with approaches that exploit either differences in relaxation times between lean and fatty tissues to generate signal intensity contrast or additional differences in resonance frequency to separate water and fat components. Typical endpoints include adipose tissue volumes and ectopic fat fractions. In recent years, all of these methods have been investigated for the characterization of brown adipose tissue morphology and metabolic activity, with chemical shift-based methods becoming more popular.

    2. Glutamate and glutamine: a review of in vivo MRS in the human brain (pages 1630–1646)

      Saadallah Ramadan, Alexander Lin and Peter Stanwell

      Article first published online: 4 OCT 2013 | DOI: 10.1002/nbm.3045

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      1. Non-invasive evaluation of glutamate and glutamine are essential for better understanding of neuroenergetics and neurotransmission.
      2. Existing 1H MRS (1D and 2D) and 13C MRS methods are reviewed and presented to the reader.
      3. Challenges are outlined and future insight into the role and evaluation of glutamate and glutamine is presented.
  3. Research articles

    1. Top of page
    2. Issue information
    3. Review articles
    4. Research articles
    1. Orientationally invariant metrics of apparent compartment eccentricity from double pulsed field gradient diffusion experiments (pages 1647–1662)

      Sune Nørhøj Jespersen, Henrik Lundell, Casper Kaae Sønderby and Tim B. Dyrby

      Article first published online: 23 AUG 2013 | DOI: 10.1002/nbm.2999

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      We propose a scheme of 60 directions, the d-PFG 5-design, for rotationally invariant sampling of double pulsed field gradient diffusion (d-PFG) MRI experiments. We introduce a metric of fractional eccentricity, shown to be equal to the fractional anisotropy of isolated water compartments.

    2. Brown adipose tissue mapping in rats with combined intermolecular double-quantum coherence and Dixon water–fat MRI (pages 1663–1671)

      Jianfeng Bao, Xiaohong Cui, Shuhui Cai, Jianhui Zhong, Congbo Cai and Zhong Chen

      Article first published online: 15 JUL 2013 | DOI: 10.1002/nbm.3000

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      A method combining intermolecular double-quantum coherence and Dixon water–fat MRI is proposed to distinguish brown adipose tissue from white adipose tissue at the cellular scale. It shows potential for the monitoring of the formation and transformation of brown adipose tissue.

    3. Reliable chemical exchange saturation transfer imaging of human lumbar intervertebral discs using reduced-field-of-view turbo spin echo at 3.0 T (pages 1672–1679)

      Qi Liu, Ning Jin, Zhaoyang Fan, Yutaka Natsuaki, Wafa Tawackoli, Gadi Pelled, Hyun Bae, Dan Gazit and Debiao Li

      Article first published online: 25 JUL 2013 | DOI: 10.1002/nbm.3001

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      Current chemical exchange saturation transfer (CEST) imaging of the lumbar intervertebral discs suffers from artifacts that prohibit accurate signal quantification, likely due to bowel movement artifacts. To improve the reliability in CEST measurement on a clinical 3.0 T scanner, a reduced field-of-view (rFOV) turbo-spin-echo (TSE) technique was developed. The proposed technique demonstrated significantly better repeatability, which allows future applications such as disc degeneration quantification.

    4. In vivo investigation of cardiac metabolism in the rat using MRS of hyperpolarized [1-13C] and [2-13C]pyruvate (pages 1680–1687)

      Sonal Josan, Jae Mo Park, Ralph Hurd, Yi-Fen Yen, Adolf Pfefferbaum, Daniel Spielman and Dirk Mayer

      Article first published online: 31 JUL 2013 | DOI: 10.1002/nbm.3003

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      This work uses hyperpolarized [2-13C]pyruvate to investigate changes in the metabolic fate of acetyl-CoA in response to DCA-induced increased PDH flux, and increased cardiac workload with dobutamine. The change in glutamate with dobutamine was observed to depend on pyruvate dose. The lower DCA-induced increase in glutamate compared with bicarbonate from [1-13C]pyruvate provides information about the relationship between PDH-mediated oxidation of pyruvate and its subsequent incorporation into the TCA cycle compared with other metabolic pathways.

    5. Quantitative magnetization transfer MRI of desmoplasia in pancreatic ductal adenocarcinoma xenografts (pages 1688–1695)

      Weiguo Li, Zhuoli Zhang, Jodi Nicolai, Guang-Yu Yang, Reed A. Omary and Andrew C. Larson

      Article first published online: 12 AUG 2013 | DOI: 10.1002/nbm.3004

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      The qMT parameter bound proton fraction (BPF) was found to be significantly higher in xenografts grown using the BxPC-3 cell line compared with the BPF for tumors grown using Panc-1 and Capan-1 cell lines. Histologic measurements showed a similar trend, with BxPC-3 tumors demonstrating significantly higher fibrosis levels compared with Panc-1 and Capan-1 tumors. BPF measurements were well correlated with quantitative fibrosis levels. Our results indicate that qMT measurements offer the potential to noninvasively quantify fibrosis levels in PDAC mouse xenograft models.

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      Hyperpolarized singlet lifetimes of pyruvate in human blood and in the mouse (pages 1696–1704)

      Irene Marco-Rius, Michael C. D. Tayler, Mikko I. Kettunen, Timothy J. Larkin, Kerstin N. Timm, Eva M. Serrao, Tiago B. Rodrigues, Giuseppe Pileio, Jan Henrik Ardenkjaer-Larsen, Malcolm H. Levitt and Kevin M. Brindle

      Article first published online: 15 AUG 2013 | DOI: 10.1002/nbm.3005

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      The 13C singlet lifetime of [1,2-13C2]pyruvate is significantly longer than the 13C T1 in human blood and in a mouse in vivo at millitesla fields. The singlet-derived NMR spectrum observed for hyperpolarized [1,2-13C2]lactate, originating from the metabolism of [1,2-13C2]pyruvate, is also examined.

    7. Effect of taxane-based neoadjuvant chemotherapy on fibroglandular tissue volume and percent breast density in the contralateral normal breast evaluated by 3T MR (pages 1705–1713)

      Jeon-Hor Chen, Wei-Fan Pan, Julian Kao, Jocelyn Lu, Li-Kuang Chen, Chih-Chen Kuo, Chih-Kai Chang, Wen-Pin Chen, Christine E. McLaren, Shadfar Bahri, Rita S. Mehta and Min-Ying Su

      Article first published online: 12 AUG 2013 | DOI: 10.1002/nbm.3006

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      This study evaluated the change of breast density in the normal breast of patients receiving taxane-based neoadjuvant chemotherapy (NAC). Forty-four breast cancer patients were studied. Our study showed that breast density measured from MR images acquired at 3T MR can be accurately quantified using a robust computer-aided algorithm based on non-parametric non-uniformity normalization (N3) and an adaptive FCM algorithm. Similarly to the AC regimen, the taxane-based regimen also caused density atrophy in the normal breast and showed reductions in fibroglandular tissue volume and percent density. The effect of breast density reduction was age related – younger patients were more likely to show a higher density reduction – and duration related.

    8. Interrelation of 31P-MRS metabolism measurements in resting and exercised quadriceps muscle of overweight-to-obese sedentary individuals (pages 1714–1722)

      Ladislav Valkovič, Barbara Ukropcová, Marek Chmelík, Miroslav Baláž, Wolfgang Bogner, Albrecht Ingo Schmid, Ivan Frollo, Erika Zemková, Iwar Klimeš, Jozef Ukropec, Siegfried Trattnig and Martin Krššák

      Article first published online: 16 AUG 2013 | DOI: 10.1002/nbm.3008

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      We showed that mitochondrial capacity, determined by the maximal oxidative flux from PCr-recovery kinetics, correlates with the Pi-to-ATP flux at rest, as well as with the creatine-kinase flux at rest in overweight-to-obese sedentary subjects. This would suggest that magnetization transfer (MT) could provide a marker of skeletal muscle metabolism that correlates with exercise–recovery experiments. We also showed that the time constant of PCr recovery correlates with MT values only if there is low variability in end-exercise pHi.

    9. Q-ball imaging with PROPELLER EPI acquisition (pages 1723–1732)

      Ming-Chung Chou, Teng-Yi Huang, Hsiao-Wen Chung, Tsyh-Jyi Hsieh, Hing-Chiu Chang and Cheng-Yu Chen

      Article first published online: 29 AUG 2013 | DOI: 10.1002/nbm.3009

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      This study employed the short-axis PROPELLER EPI technique in conjunction with data-sharing PROPELLER reconstruction to obtain QBI data with reduced susceptibility distortions. The results showed that PROPELLER EPI with affine + demon registrations substantially reduces the susceptibility distortions in PROPELLER EPI. As compared with conventional QBI, the GFA, ODF, and fiber tracts in PROPELLER QBI more closely match their anatomical locations in distortion-free TSE T2WI.

    10. Comparative evaluation of brain neurometabolites and DTI indices following whole body and cranial irradiation: a magnetic resonance imaging and spectroscopy study (pages 1733–1741)

      Mamta Gupta, Poonam Rana, Richa Trivedi, B. S. Hemanth Kumar, Ahmad Raza Khan, Ravi Soni, R. K. S. Rathore and Subash Khushu

      Article first published online: 29 AUG 2013 | DOI: 10.1002/nbm.3010

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      A combination of DTI and 1H MRS was conducted on murine brain following whole body and cranial irradiation. MRS study of the hippocampus revealed significant reduction in myoinositol and taurine metabolites in the whole body irradiated group only, whereas DTI based FA values decreased significantly in the cranial irradiated group earlier than in the whole body irradiated group. These MR techniques open new possibilities to study differential response at microstructural and metabolic levels following cranial or whole body radiation exposure.

    11. Diffusion tensor imaging detects treatment effects of FTY720 in experimental autoimmune encephalomyelitis mice (pages 1742–1750)

      Xiaojie Wang, Joan K. Brieland, Joong H. Kim, Ying-Jr Chen, Janet O'Neal, Shawn P. O'Neil, Tsang-Wei Tu, Kathryn Trinkaus and Sheng-Kwei Song

      Article first published online: 12 AUG 2013 | DOI: 10.1002/nbm.3012

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      Prophylactic administration of FTY720 prevented axon and myelin damage when compared with EAE mice without treatment. Therapeutic treatment of FTY720 reduced the disease severity, improving the axial and radial diffusivity towards the control values without statistical significance. The in vivo DTI-derived axial and radial diffusivity correlated with clinical scores in EAE mice. The results support the use of in vivo DTI as an effective outcome measure for preclinical drug development.

    12. Rapid hybrid encoding for high-resolution whole-brain fluid-attenuated imaging (pages 1751–1761)

      Hoonjae Lee, Chul-Ho Sohn and Jaeseok Park

      Article first published online: 3 SEP 2013 | DOI: 10.1002/nbm.3013

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      We introduce a novel, rapid hybrid encoding method for highly efficient whole-brain fluid-attenuated imaging in a clinically reasonable imaging time for lesion detection in white matter diseases. Volumetric data are continuously encoded using hybrid modular acquisition (PSIF: high frequency; TSE: low frequency) in a sequential fashion throughout signal transition during inversion recovery. In vivo studies demonstrate that, compared with conventional FLAIR, the proposed method substantially speeds up imaging time with little loss of signal-to-noise ratio while retaining lesion conspicuity.

    13. Diffusion-weighted MRI monitoring of pancreatic cancer response to radiofrequency heat-enhanced intratumor chemotherapy (pages 1762–1767)

      Tong Zhang, Feng Zhang, Yanfeng Meng, Han Wang, Thomas Le, Baojie Wei, Donghoon Lee, Patrick Willis, Baozhong Shen and Xiaoming Yang

      Article first published online: 4 SEP 2013 | DOI: 10.1002/nbm.3014

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      Apparent diffusion coefficient (ADC) measurements indicate that the change in ADC value is a sensitive biomarker of the physiological response to hyperthermia-mediated chemotherapy of pancreatic cancers.

    14. Effects of fat on MR-measured metabolite signal strengths: implications for in vivo MRS studies of the human brain (pages 1768–1774)

      Anderson Mon, Christoph Abé, Timothy C. Durazzo and Dieter J. Meyerhoff

      Article first published online: 24 SEP 2013 | DOI: 10.1002/nbm.3016

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      MR-measured metabolite signals of the brain decreased in the presence of fat. The reduced metabolite signals in the presence of fat are reminiscent of the negative associations observed between BMI and in vivo MR-measured metabolite levels. This physical effect of fat on MR-measured brain metabolite signals may have far-reaching consequences for the accuracy of in vivo MR measurements of brain metabolite concentration and their interpretation.

    15. Determination of the appropriate b value and number of gradient directions for high-angular-resolution diffusion-weighted imaging (pages 1775–1786)

      J.-Donald Tournier, Fernando Calamante and Alan Connelly

      Article first published online: 29 AUG 2013 | DOI: 10.1002/nbm.3017

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      We estimated the minimum number of diffusion-weighted (DW) directions and optimal b value required for high-angular-resolution diffusion-weighted imaging (HARDI) by focusing on the angular frequencies in the DW signal, using spherical harmonics. Using 500 DW direction data, we found terms above l = 8 to be negligible in practice for b ≤ 5000 s/mm2, implying that 45 DW directions are sufficient. l > 0 terms were found to increase with b value and to level off at b = 3000 s/mm2, suggesting that this provides the highest achievable angular resolution.

    16. Modeling of the diffusion MR signal in calibrated model systems and nerves (pages 1787–1795)

      Darya Morozov, Leah Bar, Nir Sochen and Yoram Cohen

      Article first published online: 16 SEP 2013 | DOI: 10.1002/nbm.3018

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      Diffusion NMR is an important means of obtaining microstructural information. We demonstrate that our modeling of single-pulsed-field gradient (s-PFG) MR experiments performed on model systems of increasing complexity, in which the ground truth is known, can identify the number of restricted compartments, detect their sizes and determine their relative populations, without prior assumptions with regard to the number of compartments. Moreover, the model can identify free diffusion when present in addition to the restricted compartments. This model was used to study the microstructure of excised nerves.

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      Coil combination of multichannel MRSI data at 7 T: MUSICAL (pages 1796–1805)

      B. Strasser, M. Chmelik, S. D. Robinson, G. Hangel, S. Gruber, S. Trattnig and W. Bogner

      Article first published online: 4 SEP 2013 | DOI: 10.1002/nbm.3019

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      A new coil combination method for MRSI data using a matching imaging scan is proposed. The method increases the signal-to-noise ratio, and decreases the Cramér–Rao lower bounds or reduces the algorithm complexity and hardware demands relative to available standard methods, i.e. using the first free induction decay (FID) point, or using sensitivity maps as weights. The proposed method performed well at 7 T using a FID-based MRSI sequence with a matching gradient echo imaging sequence, but could also be extended to other field strengths and sequences.

    18. Assessment of diffusion parameters by intravoxel incoherent motion MRI in head and neck squamous cell carcinoma (pages 1806–1814)

      Simona Marzi, Francesca Piludu and Antonello Vidiri

      Article first published online: 30 AUG 2013 | DOI: 10.1002/nbm.3020

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      Different approaches to the tumor region of interest selection and different numerical methods to extract intravoxel incoherent motion (IVIM) diffusion parameters were implemented and compared in a group of patients with head and neck squamous cell carcinoma. The largest tumor section was found to be representative of the entire tumor volume. Our results suggest that a simplified IVIM acquisition protocol could be defined, with a reduced number of b values in the low b value range, to assess the perfusion fraction. The apparent diffusion coefficient and IVIM diffusion parameters were dependent on the anatomic site of the lesion.

    19. MR imaging of protein folding in vitro employing Nuclear-Overhauser-mediated saturation transfer (pages 1815–1822)

      Moritz Zaiss, Patrick Kunz, Steffen Goerke, Alexander Radbruch and Peter Bachert

      Article first published online: 25 SEP 2013 | DOI: 10.1002/nbm.3021

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      Urea-dependent unfolding of bovine serum albumin (BSA), which can be monitored by fluorescence spectroscopy, affects saturation transfer between water and aliphatic protons of the protein mediated by dipole–dipole couplings (nuclear Overhauser effect, NOE). We show in vitro at 7 T that the NOE imaging contrast of the BSA solution is a function of protein structure and propose that, besides concentration, temperature and pH, protein folding/unfolding generates an additional contrast mechanism of CEST MRI.

    20. You have full text access to this OnlineOpen article
      Tissue- and column-specific measurements from multi-parameter mapping of the human cervical spinal cord at 3 T (pages 1823–1830)

      R. S. Samson, O. Ciccarelli, C. Kachramanoglou, L. Brightman, A. Lutti, D. L. Thomas, N. Weiskopf and C. A. M. Wheeler-Kingshott

      Article first published online: 16 SEP 2013 | DOI: 10.1002/nbm.3022

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      Using this method, a range of MR parameters [apparent proton density (APD), T1, magnetisation transfer ratio (MTR), MT and R2*] in the white matter columns and grey matter of the healthy cervical cord can be quantified in vivo in just 20 min. This technique has the potential to provide an insight into pathological processes occurring in the cervical cord affected by neurological disorders.

    21. Hyperpolarized 13C NMR studies of glucose metabolism in living breast cancer cell cultures (pages 1831–1843)

      T. Harris, H. Degani and L. Frydman

      Article first published online: 24 SEP 2013 | DOI: 10.1002/nbm.3024

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      New ways of monitoring glycolytic processes in live breast cancer cell cultures based on perdeuterated hyperpolarized glucose are demonstrated (a). Lactate and other intermediates are then visible on T47D cells maintained viable in a custom-made continuous bioreactor (b). Metabolic characteristics of other ‘invisible’ intermediates can also be gathered from saturation transfer experiments (c).

    22. You have full text access to this OnlineOpen article
      Cerebral blood flow response to acute hypoxic hypoxia (pages 1844–1852)

      Ashley D. Harris, Kevin Murphy, Claris M. Diaz, Neeraj Saxena, Judith E. Hall, Thomas T. Liu and Richard G. Wise

      Article first published online: 7 OCT 2013 | DOI: 10.1002/nbm.3026

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      The temporal responses of the cerebral blood flow (CBF) and R2* to hypoxic hypoxia were quantified in grey matter across the whole brain and regionally in healthy volunteers. The R2* increase confirmed a rapid decrease in blood oxygenation, whereas the hypoxia-induced increase in CBF took longer, on the order of 3 min. On return to normoxia, both R2* and the CBF responses were more rapid than during the transition to hypoxia; however, the CBF response was still slower than the R2* response.

    23. Quantitative susceptibility mapping of kidney inflammation and fibrosis in type 1 angiotensin receptor-deficient mice (pages 1853–1863)

      Luke Xie, Matthew A. Sparks, Wei Li, Yi Qi, Chunlei Liu, Thomas M. Coffman and G. Allan Johnson

      Article first published online: 24 OCT 2013 | DOI: 10.1002/nbm.3039

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      Quantitative susceptibility mapping (QSM) was very sensitive in detecting inflamed and fibrotic lesions in the kidney (confirmed by histology and indicated by yellow arrows); QSM was able to resolve pathological detail better than its magnitude image counterpart. Focal lesions of inflammation and fibrosis were segmented and found to be closely associated with major vessels (indicated by a yellow arrow in the volume render). Susceptibilities were more diamagnetic, which is consistent with the increase in diamagnetic content, e.g. proteins and lipids, associated with inflammation and fibrosis.

    24. High-resolution MRI of uveal melanoma using a microcoil phased array at 7 T (pages 1864–1869)

      J. W. M. Beenakker, G. A. van Rijn, G. P. M. Luyten and A. G. Webb

      Article first published online: 7 OCT 2013 | DOI: 10.1002/nbm.3041

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      A three-element microcoil phased array was constructed as a high-sensitivity receive-only device for ocular imaging at 7 T. Using a dedicated blink/fixation protocol, high-resolution in vivo images could be acquired within 3 min in volunteers and patients. In a patient with uveal melanoma, in vivo MRI gave excellent tumour/aqueous body contrast, and ex vivo imaging of the enucleated eye showed significant heterogeneity within the tumour.

    25. Cell layers and neuropil: contrast-enhanced MRI of mouse brain in vivo (pages 1870–1878)

      Takashi Watanabe, Jens Frahm and Thomas Michaelis

      Article first published online: 21 OCT 2013 | DOI: 10.1002/nbm.3042

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      Contrast-enhanced T1-weighted MRI at 9.4 T and an in-plane resolution of 25 µm has been demonstrated to differentiate neural tissues in mouse brain in vivo, including granule cell layers, principal cell layers, general neuropil, specialized neuropil and white matter. Contrast caused by the intracranial administration of gadopentetate dimeglumine (Gd-DTPA) reflects the extra- and intracellular spaces of gray matter and highlights the general neuropil areas. Systemic administration of manganese chloride highlights the principal cell layers and the specialized neuropil areas.

    26. q-Space diffusion MRI (QSI) of the disease progression in the spinal cords of the Long Evans shaker: diffusion time and apparent anisotropy (pages 1879–1886)

      Debbie Anaby, Ian D. Duncan, Chelsey M. Smith and Yoram Cohen

      Article first published online: 9 OCT 2013 | DOI: 10.1002/nbm.3043

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      q-Space diffusion MRI was performed on excised spinal cords of Long Evans shaker (les) rats and their controls during maturation at different diffusion times. QSI indices were able to report on the les pathology in all age groups, and the differences between the les and control spinal cords were found to be more apparent at long diffusion times. It was found that the radial diffusivity was a better index than the fractional anisotropy (FA) for observing les pathology. As the diffusion time was found to affect not only the diffusion characteristics in the two groups, but also the diffusion anisotropy, it is suggested that the term apparent anisotropy should be used.