In Vivo Monitoring of Rat Spinal Cord Metabolism Using Hyperpolarized Carbon-13 MR Spectroscopic Imaging.

This study demonstrated the feasibility of using hyperpolarized 13C-MR spectroscopic imaging with [1-13C]-pyruvate to evaluate in vivo spinal cord metabolism. High pyruvate and relatively small lactate signal were observed in the cervical spinal cords of naive rats. Lactate and pyruvate measures were similar for spinal cord and supratentorial brain. The results from this study establish baseline measures for spinal cord hyperpolarized MRS imaging with 13C pyruvate. This technique holds promise as a valuable molecular imaging tool for monitoring biochemical processes in the normal and diseased spinal cord.

Quantitative 7T phase imaging in premanifest Huntington disease.

BACKGROUND AND PURPOSE: In vivo MR imaging and postmortem neuropathologic studies have demonstrated elevated iron concentration and atrophy within the striatum of patients with Huntington disease, implicating neuronal loss and iron accumulation in the pathogenesis of this neurodegenerative disorder. We used 7T MR imaging to determine whether quantitative phase, a measurement that reflects both iron content and tissue microstructure, is altered in subjects with premanifest Huntington disease. MATERIALS AND METHODS: Local field shift, calculated from 7T MR phase images, was quantified in 13 subjects with premanifest Huntington disease and 13 age- and sex-matched controls. All participants underwent 3T and 7T MR imaging, including volumetric T1 and 7T gradient recalled-echo sequences. Local field shift maps were created from 7T phase data and registered to caudate ROIs automatically parcellated from the 3T T1 images. Huntington disease-specific disease burden and neurocognitive and motor evaluations were also performed and compared with local field shift. RESULTS: Subjects with premanifest Huntington disease had smaller caudate volume and higher local field shift than controls. A significant correlation between these measurements was not detected, and prediction accuracy for disease state improved with inclusion of both variables. A positive correlation between local field shift and genetic disease burden was also found, and there was a trend toward significant correlations between local field shift and neurocognitive tests of working memory and executive function. CONCLUSIONS: Subjects with premanifest Huntington disease exhibit differences in 7T MR imaging phase within the caudate nuclei that correlate with genetic disease burden and trend with neurocognitive assessments. Ultra-high-field MR imaging of quantitative phase may be a useful approach for monitoring neurodegeneration in premanifest Huntington disease.

Stable isotopes document resource partitioning and effects of forest disturbance on sympatric cheirogaleid lemurs.

The future of Madagascar's forests and their resident lemurs is precarious. Determining how species respond to forest fragmentation is essential for management efforts. We use stable isotope biogeochemistry to investigate how disturbance affects resource partitioning between two genera of cheirogaleid lemurs (Cheirogaleus and Microcebus) from three humid forest sites: continuous and fragmented forest at Tsinjoarivo, and selectively logged forest at Ranomafana. We test three hypotheses: (H1) cheirogaleids are unaffected by forest fragmentation, (H2) species respond individually to disturbance and may exploit novel resources in fragmented habitat, and (H3) species alter their behavior to rely on the same key resource in disturbed forest. We find significant isotopic differences among species and localities. Carbon data suggest that Microcebus feed lower in the canopy than Cheirogaleus at all three localities and that sympatric Cheirogaleus crossleyi and C. sibreei feed at different canopy heights in the fragmented forest. Microcbus have higher nitrogen isotope values than Cheirogaleus at all localities, indicating more faunivory. After accounting for baseline isotope values in plants, our results provide the most support for H3. We find similar isotopic variations among localities for both genera. Small differences in carbon among localities may reflect shifts in diet or habitat use. Elevated nitrogen values for cheirogaleid lemurs in fragments may reflect increased arthropod consumption or nutritional stress. These results suggest that cheirogaleids are affected by forest disturbance in Eastern Madagascar and stress the importance of accounting for baseline isotopic differences in plants in any work comparing localities.

Super-resolution track density imaging of glioblastoma: histopathologic correlation.

BACKGROUND AND PURPOSE: Super-resolution track density imaging generates anatomic images with submillimeter voxel resolution by using high-angular-resolution diffusion imaging and fiber-tractography. TDI within the diseased human brain has not been previously described. The purpose of this study was to correlate TDI with histopathologic features of GBM. MATERIALS AND METHODS: A total of 43 tumor specimens (24 contrast-enhancing, 12 NE, and 7 centrally necrotic regions) were collected from 18 patients with treatment-naïve GBM by use of MR imaging-guided neurosurgical techniques. Immunohistochemical stains were used to evaluate the following histopathologic features: hypoxia, architectural disruption, microvascular hyperplasia, and cellular proliferation. We reconstructed track density maps at a 0.25-mm isotropic spatial resolution by using probabilistic streamline tractography combined with constrained spheric deconvolution (model order, 8; 0.1-mm step size; 1 million seed points). Track density values were obtained from each tissue site. A P value of .05 was considered significant and was adjusted for multiple comparisons by use of the false discovery rate method. RESULTS: Track density was not significantly different between contrast-enhancing and NE regions but was more likely to be elevated within regions demonstrating aggressive histopathologic features (P < .05). Significant correlation between relative track density and hypoxia (odds ratio, 3.52; P = .01), architectural disruption (odds ratio, 3.49; P = .03), and cellular proliferation (odds ratio, 1.70; P = .05) was observed irrespective of the presence or absence of contrast enhancement. CONCLUSIONS: Numeric values of track density correlate with GBM biologic features and may be clinically useful for identification of regions of tumor infiltration within both enhancing and NE components of GBM.

Hippocampal CA1 apical neuropil atrophy in mild Alzheimer disease visualized with 7-T MRI.

OBJECTIVES: In Alzheimer disease (AD), mounting evidence points to a greater role for synaptic loss than neuronal loss. Supporting this notion, multiple postmortem studies have demonstrated that the hippocampal CA1 apical neuropil is one of the earliest sites of pathology, exhibiting tau aggregates and then atrophy before there is substantial loss of the CA1 pyramidal neurons themselves. In this cross-sectional study, we tested whether tissue loss in the CA1 apical neuropil layer can be observed in vivo in patients with mild AD. METHODS: We performed ultra-high-field 7-T MRI on subjects with mild AD (n = 14) and age-matched normal controls (n = 16). With a 2-dimensional T2*-weighted gradient-recalled echo sequence that was easily tolerated by subjects, we obtained cross-sectional slices of the hippocampus at an in-plane resolution of 195 µm. RESULTS: On images revealing the anatomic landmarks of hippocampal subfields and strata, we observed thinning of the CA1 apical neuropil in subjects with mild AD compared to controls. By contrast, the 2 groups exhibited no difference in the thickness of the CA1 cell body layer or of the entire CA1 subfield. Hippocampal volume, measured on a conventional T1-weighted sequence obtained at 3T, also did not differentiate these patients with mild AD from controls. CONCLUSIONS: CA1 apical neuropil atrophy is apparent in patients with mild AD. With its superior spatial resolution, 7-T MRI permits in vivo analysis of a very focal, early site of AD pathology.

Imaging considerations for in vivo 13C metabolic mapping using hyperpolarized 13C-pyruvate.

One of the challenges of optimizing signal-to-noise ratio (SNR) and image quality in (13)C metabolic imaging using hyperpolarized (13)C-pyruvate is associated with the different MR signal time-courses for pyruvate and its metabolic products, lactate and alanine. The impact of the acquisition time window, variation of flip angles, and order of phase encoding on SNR and image quality were evaluated in mathematical simulations and rat experiments, based on multishot fast chemical shift imaging (CSI) and three-dimensional echo-planar spectroscopic imaging (3DEPSI) sequences. The image timing was set to coincide with the peak production of lactate. The strategy of combining variable flip angles and centric phase encoding (cPE) improved image quality while retaining good SNR. In addition, two aspects of EPSI sampling strategies were explored: waveform design (flyback vs. symmetric EPSI) and spectral bandwidth (BW = 500 Hz vs. 267 Hz). Both symmetric EPSI and reduced BW trended toward increased SNR. The imaging strategies reported here can serve as guidance to other multishot spectroscopic imaging protocols for (13)C metabolic imaging applications.

Genotype-Phenotype correlations in multiple sclerosis: HLA genes influence disease severity inferred by 1HMR spectroscopy and MRI measures.

Genetic susceptibility to multiple sclerosis (MS) is associated with the human leukocyte antigen (HLA) DRB1*1501 allele. Here we show a clear association between DRB1*1501 carrier status and four domains of disease severity in an investigation of genotype-phenotype associations in 505 robust, clinically well characterized MS patients evaluated cross-sectionally: (i) a reduction in the N-acetyl-aspartate (NAA) concentration within normal appearing white matter (NAWM) via (1)HMR spectroscopy (P = 0.025), (ii) an increase in the volume of white matter (WM) lesions utilizing conventional anatomical MRI techniques (1,127 mm(3); P = 0.031), (iii) a reduction in normalized brain parenchymal volume (nBPV) (P = 0.023), and (iv) impairments in cognitive function as measured by the Paced Auditory Serial Addition Test (PASAT-3) performance (Mean Z Score: DRB1*1501+: 0.110 versus DRB1*1501-: 0.048; P = 0.004). In addition, DRB1*1501+ patients had significantly more women (74% versus 63%; P = 0.009) and a younger mean age at disease onset (32.4 years versus 34.3 years; P = 0.025). Our findings suggest that DRB1*1501 increases disease severity in MS by facilitating the development of more T2-foci, thereby increasing the potential for irreversible axonal compromise and subsequent neuronal degeneration, as suggested by the reduction of NAA concentrations in NAWM, ultimately leading to a decline in brain volume. These structural aberrations may explain the significant differences in cognitive performance observed between DRB1*1501 groups. The overall goal of a deep phenotypic approach to MS is to develop an array of meaningful biomarkers to monitor the course of the disease, predict future disease behaviour, determine when treatment is necessary, and perhaps to more effectively recommend an available therapeutic intervention.

DNP-Hyperpolarized C Magnetic Resonance Metabolic Imaging for Cancer Applications.

Critical factors in characterizing the aggressiveness and response to therapy for tumors are the availability of noninvasive biomarkers that can be combined with other clinical parameters to tailor treatment regimens to each individual patient. While conventional magnetic resonance (MR) images are widely used to estimate changes in tumor size, they do not provide the rapid readout that is required to make an early decision on whether a change in therapy is required. The use of hyperpolarized (13)C agents to obtain metabolic imaging data is of great interest for in vivo assessment of tumors. One of the first agents being considered for in vivo studies with dynamic nuclear polarization (DNP) is 1-(13)C-labeled pyruvate, which is converted to lactate or alanine, dependent upon the needs of the tissue in question. The development of this new technology and its implementation in preclinical cancer model systems has clearly demonstrated the potential for highlighting tumor aggressiveness and for monitoring changes associated with disease progression. While there is further work to do in terms of studying new agents, improving the DNP process itself and developing efficient MR methods for acquiring and analyzing the data, the preliminary results are extremely promising and provide strong motivation for considering cancer as one of the first applications of the technology.

Analysis of metabolic indices in regions of abnormal perfusion in patients with high-grade glioma.

BACKGROUND AND PURPOSE: MR spectroscopic imaging (MRSI) and dynamic susceptibility-contrast MR imaging (DSC-MR imaging) are functional in vivo techniques for assessing tumor metabolism and vasculature characteristics. Because tumor hypoxia is influenced by tortuous, degraded, swollen, and angiogenic tumor vasculature, regions of abnormal perfusion parameters should coexist with changes in lactate and creatine metabolite levels. MATERIALS AND METHODS: DSC-MR imaging and lactate-edited MRSI were performed on 38 treatment-naive patients with high-grade gliomas (17 grade III, 21 grade IV) before surgical diagnosis. Regions of abnormal perfusion were determined from peak height and percent recovery maps for each voxel within the spectroscopic imaging volume. Choline, creatine, and lactate levels within voxels experiencing only abnormal peak height (aPH), only abnormal recovery (aRec), and both abnormal peak height and recovery (aPH+aRec) were determined and compared to the surrounding T2 hyperintensity (T2h) and normal-appearing white matter. RESULTS: There were decreasing trends in volume from aPH to aRec to aPH+aRec regions for both grade III and grade IV gliomas. Grade IV gliomas exhibited significantly elevated choline in all abnormal perfusion regions, with reduced creatine and increased lactate in the aRec region relative to the surrounding T2h. Grade III gliomas showed trends toward increased creatine within the aPH region and reduced levels within the aRec region. CONCLUSION: Depressed creatine and elevated lactate levels confirmed the lack of oxygenation within regions of compromised vascular integrity. Identification of regions with leaky or dense vasculature and metabolic markers of hypoxia and cellular proliferation could be useful in determining the more aggressive part of the tumor for targeting, monitoring, and assessing effects of treatment.

Estimation of metabolite T1 relaxation times using tissue specific analysis, signal averaging and bootstrapping from magnetic resonance spectroscopic imaging data.

OBJECT: A novel method of estimating metabolite T1 relaxation times using MR spectroscopic imaging (MRSI) is proposed. As opposed to conventional single-voxel metabolite T1 estimation methods, this method investigates regional and gray matter (GM)/white matter (WM) differences in metabolite T1 by taking advantage of the spatial distribution information provided by MRSI. MATERIAL AND METHODS: The method, validated by Monte Carlo studies, involves a voxel averaging to preserve the GM/WM distribution, a non-linear least squares fit of the metabolite T1 and an estimation of its standard error by bootstrapping. It was applied in vivo to estimate the T1 of N-acetyl compounds (NAA), choline, creatine and myo-inositol in eight normal volunteers, at 1.5 T, using a short echo time 2D-MRSI slice located above the ventricles. RESULTS: WM-T 1,NAA was significantly (P < 0.05) longer in anterior regions compared to posterior regions of the brain. The anterior region showed a trend of a longer WM T1 compared to GM for NAA, creatine and myo-Inositol. Lastly, accounting for the bootstrapped standard error estimate in a group mean T1 calculation yielded a more accurate T1 estimation. CONCLUSION: The method successfully measured in vivo metabolite T1 using MRSI and can now be applied to diseased brain.

Differentiation of glioblastoma multiforme and single brain metastasis by peak height and percentage of signal intensity recovery derived from dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging.

BACKGROUND AND PURPOSE: Glioblastoma multiforme (GBM) and single brain metastasis (MET) are the 2 most common malignant brain tumors that can appear similar on anatomic imaging but require vastly different treatment strategy. The purpose of our study was to determine whether the peak height and the percentage of signal intensity recovery derived from dynamic susceptibility-weighted contrast-enhanced (DSC) perfusion MR imaging could differentiate GBM and MET. MATERIALS AND METHODS: Forty-three patients with histopathologic diagnosis of GBM (n=27) or MET (n=16) underwent DSC perfusion MR imaging in addition to anatomic MR imaging before surgery. Regions of interest were drawn around the nonenhancing peritumoral T2 lesion (PTL) and the contrast-enhancing lesion (CEL). T2* signal intensity-time curves acquired during the first pass of gadolinium contrast material were converted to the changes in relaxation rate to yield T2* relaxivity (Delta R2*) curve. The peak height of maximal signal intensity drop and the percentage of signal intensity recovery at the end of first pass were measured for each voxel in the PTL and CEL regions of the tumor. RESULTS: The average peak height for the PTL was significantly higher (P=.04) in GBM than in MET. The average percentage of signal intensity recovery was significantly reduced in PTL (78.4% versus 82.8%; P=.02) and in CEL (62.5% versus 80.9%, P<.01) regions of MET compared with those regions in the GBM group. CONCLUSIONS: The findings of our study show that the peak height and the percentage of signal intensity recovery derived from the Delta R2* curve of DSC perfusion MR imaging can differentiate GBM and MET.

Landscape controls on mercury in streamwater at Acadia National Park, USA.

Fall and spring streamwater samples were analyzed for total mercury (Hg) and major ions from 47 locations on Mount Desert Island in Maine. Samples were collected in zones that were burned in a major wildfire in 1947 and in zones that were not burned. We hypothesized that Hg concentrations in streamwater would be higher from unburned sites than burned watersheds, because fire would volatilize stored Hg. The Hg concentrations, based on burn history, were not statistically distinct. However, significant statistical associations were noted between Hg and the amount of wetlands in the drainage systems and with streamwater dissolved organic carbon (DOC). An unexpected result was that wetlands mobilized more Hg by generating more DOC in total, but upland DOC was more efficient at transporting Hg because it transports more Hg per unit DOC. Mercury concentrations were higher in samples collected at lower elevations. Mercury was positively correlated with relative discharge, although this effect was not distinguished from the DOC association. In this research, sample site elevation and the presence of upstream wetlands and their associated DOC affected Hg concentrations more strongly than burn history.

Mass balances of mercury and nitrogen in burned and unburned forested watersheds at Acadia National Park, Maine, USA.

Precipitation and streamwater samples were collected from 16 November 1999 to 17 November 2000 in two watersheds at Acadia National Park, Maine, and analyzed for mercury (Hg) and dissolved inorganic nitrogen (DIN, nitrate plus ammonium). Cadillac Brook watershed burned in a 1947 fire that destroyed vegetation and soil organic matter. We hypothesized that Hg deposition would be higher at Hadlock Brook (the reference watershed, 10.2 microg/m(2)/year) than Cadillac (9.4 microg/m(2)/year) because of the greater scavenging efficiency of the softwood vegetation in Hadlock. We also hypothesized the Hg and DIN export from Cadillac Brook would be lower than Hadlock Brook because of elemental volatilization during the fire, along with subsequently lower rates of atmospheric deposition in a watershed with abundant bare soil and bedrock, and regenerating vegetation. Consistent with these hypotheses, Hg export was lower from Cadillac Brook watershed (0.4 microg/m(2)/year) than from Hadlock Brook watershed (1.3 microg/m(2)/year). DIN export from Cadillac Brook (11.5 eq/ha/year) was lower than Hadlock Brook (92.5 eq/ha/year). These data show that approximately 50 years following a wildfire there was lower atmospheric deposition due to changes in forest species composition, lower soil pools, and greater ecosystem retention for both Hg and DIN.

Paleoecological assessment of watershed history in PRIMENet watersheds at Acadia National Park, USA.

Paleoecological reconstructions of forest stand histories for two upland watersheds at Acadia National Park in Maine were completed to support related watershed chemistry studies. The project hypothesis was that forest type and fire history influence long-term cycling and storage of atmospheric mercury and nitrogen within watersheds. The reconstructions document differences in major vegetation composition and disturbance between the burned and unburned watersheds during the past several centuries. Pollen and charcoal stratigraphies from organic sediment accumulations in forested wet depressions indicate that the present experimental design of contrasting disturbance and forest histories has persisted during recent centuries. The unburned watershed has been dominated by spruce (Picea rubens) and fir (Abies balsamea) for 500 years or more and has not recently burned or been substantially cleared. The burned watershed is dominated by a heterogeneous forest of patchy hardwood, mixed wood, and softwood stands. A large portion of this watershed burned severely in 1947 and probably more than once in the 1800s, and has supported heterogeneous successional forests for 200 years or longer. Overall, these results support the underlying premise that the experimental design of this watershed research can be used to infer landscape controls on biogeochemical processes.

Watershed nitrogen and mercury geochemical fluxes integrate landscape factors in long-term research watersheds at Acadia National Park, Maine, USA.

This paper is an overview of this special issue devoted to watershed research in Acadia National Park (Acadia NP). The papers address components of an integrated research program on two upland watersheds at Acadia NP, USA (44 degrees 20' N latitude; 68 degrees 15' E longitude). These watersheds were instrumented in 1998 to provide a long-term foundation for regional ecological and watershed research. The research was initiated as part of EPA/NPS PRIMENet (Park Research and Intensive Monitoring of Ecosystems Network), a system of UV-monitoring stations and long-term watershed research sites located in US national parks. The initial goals at Acadia NP were to address research questions about mercury, acid rain, and nitrogen saturation developed from prior research. The project design was based on natural differences in forests and soils induced by an intense wildfire in one watershed in 1947. There is no evidence of fire in the reference watershed for several hundred years. We are testing hypotheses about controls on surface water chemistry, and bioavailability of contaminants in the contrasting watersheds. The unburned 47-ha Hadlock Brook watershed is 70% spruce-fir mature conifer forest. In contrast, burned 32-ha Cadillac Brook watershed, 4 km northeast of the Hadlock watershed, is 20% regenerating mixed northern hardwoods and 60% shrub/rocky balds. Differences in atmospheric deposition are controlled primarily by forest stand composition and age. The watersheds are gauged and have water chemistry stations at 122 m (Cadillac) and 137 m (Hadlock); watershed maximum elevations are 468 and 380 m, respectively. The stream water chemistry patterns reflect, in part, the legacy of the intense fire, which, in turn, controls differences in forest vegetation and soil characteristics. These factors result in higher nitrogen and mercury flux from the unburned watershed, reflecting differences in atmospheric deposition, contrasting ecosystem pools of nitrogen and mercury, and inferred differences in internal cycling and bioavailabilty.

In vivo 31P MR spectral patterns and reproducibility in cancer patients studied in a multi-institutional trial.

The standardization and reproducibility of techniques required to acquire anatomically localized 31P MR spectra non-invasively while studying tumors in cancer patients in a multi-institutional group at 1.5 T are reported. This initial group of patients was studied from 1995 to 2000 to test the feasibility of acquiring in vivo localized 31P MRS in clinical MR spectrometers. The cancers tested were non-Hodgkin's lymphomas, sarcomas of soft tissue and bone, breast carcinomas and head and neck carcinomas. The best accrual and spectral quality were achieved with the non-Hodgkin's lymphomas. The initial analysis of the spectral values of the sum of phosphoethanolamine plus phosphocholine normalized by the content of nucleotide triphosphates in a homogeneous sample of 32 NHL patients studied by in vivo (31)P MRS showed good reproducibility among different institutions. No statistical differences were found between the institution with the largest number of cases accrued and the rest of the multi-institutional NHL data (2.28 +/- 0.64, mean +/- standard error; n = 17, vs 2.08 +/- 0.14, n = 15). The preliminary data reported demonstrate that the institutions involved in this trial are obtaining reproducible 31P MR spectroscopic data non-invasively from human tumors. This is a fundamental prerequisite for the international cooperative group to be able to demonstrate the clinical value of the normalized determination of phosphoethanolamine plus phosphocholine by 31P MRS as predictor for treatment response in cancer patients.

Estimation of critical loads of acidity for lakes in northeastern United States and eastern Canada.

The New England Governors and Eastern Canadian Premiers (NEG/ECP) adopted the Acid Rain Action Plan in June 1998, and issued a series of action items to support its work toward a reduction of sulfur dioxide (SO(2)) and nitrogen oxide (NO(x)) emissions in northeastern North America. One of these action items was the preparation of an updated critical load map using data from lakes in the NEG/ECP area. Critical load maps provide a more complete index of the surface water sensitivity to acidification. Combined sulfur and nitrogen critical loads and deposition exceedances were computed using Henriksen's Steady-State Water Chemistry (SSWC) model. Results show that 28% of all 2053 lakes studied have a critical load of 20 kg/ha/year or less, making them vulnerable to acid deposition. Emission reductions, and more specifically SO(2) emission reductions have proven beneficial because critical loads were exceeded in 2002 for 12.3% of all studied lakes. Those lakes are located in the more sensitive areas where geology is carbonate-poor. Of these lakes, 2.9% will never recover even with a complete removal of SO(4) deposition. Recovery from acidification for the remaining 9.4% of the lakes will require additional emission SO(2) reductions.

Methodological standardization for a multi-institutional in vivo trial of localized 31P MR spectroscopy in human cancer research. In vitro and normal volunteer studies.

A multi-institutional group has been created to demonstrate the utility of in vivo 31P magnetic resonance spectroscopy (31P-MRS) to study human cancers in vivo. This review is concerned with the novel problems concerning quality control in this large multinational trial of 31P MRS. Our results show that the careful and systematic performance of the quality control tests depicted here (standardized dual 1H/31P tuned radiofrequency probe, quality control procedures, routine use of 1H irradiation while acquiring 31P MR signals) has ensured comparable results between the different institutions. In studies made in vitro, the root-mean-square error was 3.6 %, and in muscle of healthy volunteers in vivo the coefficients of variance for the ratios phosphocreatine/nucleotide-triphosphates, phosphocreatine/noise and nucleotide-triphosphate/noise were 12.2, 7.0 and 10.8 %, respectively. The standardization of the acquisition protocol for in vivo-localized 31P MR spectroscopy across the different institutions has resulted in comparable in vivo data, decreasing the possible problems related to a research study carried out under a multi-institutional setting.

Mechanisms of normal appearing corpus callosum injury related to pericallosal T1 lesions in multiple sclerosis using directional diffusion tensor and 1H MRS imaging.

OBJECTIVES: To investigate the extent of tissue damage in a region of normal appearing corpus callosum (NACC) for different forms of multiple sclerosis (MS) using diffusion tensor and proton magnetic resonance (MR) spectroscopic imaging. METHODS: A total of 47 patients with MS and 15 controls were included. Regions of interest from the NACC were manually segmented using high resolution anatomical images. Diffusion tensor eigenvalues and metabolite ratio of N-acetyl-aspartate (NAA) to creatine/phosphocreatine (Cr) were calculated in the NACC region. RESULTS: Increased apparent diffusion coefficients (ADCs) and decreased anisotropy were observed in the NACC for patients with MS relative to the control subjects. These resulted from increased diffusion tensor eigenvalues perpendicular to the maximum diffusion direction. The NAA:Cr ratio was decreased in the NACC for patients with MS relative to the control subjects. Significant correlations between pericallosal T1 lesion load and MR modalities in the NACC were observed for patients with relapsing remitting/secondary progressive MS (RR/SPMS), but not for patients with primary progressive MS (PPMS). CONCLUSION: This study provides further insight into changes in the ADC and diffusion anisotropy based on the diffusion tensor eigenvalues for patients with MS. The changes in the diffusion tensor eigenvalues and NAA:Cr ratio in the NACC for patients with RR/SPMS suggest axonal injury and/or dysfunction induced by wallerian degeneration. The lack of correlation between these variables in the NACC and focal MS lesions for patients with PPMS further supports intrinsic differences related to tissue injury between these subtypes of MS.

MRI lesion volume heterogeneity in primary progressive MS in relation with axonal damage and brain atrophy.

OBJECTIVES: To investigate whether axonal damage in primary progressive (PP) multiple sclerosis (MS), as measured by proton magnetic resonance spectroscopy (HMRS) imaging and brain atrophy, is a function of T2 weighted brain lesion volume. METHODS: 34 PP MS patients were divided into two categories: low (<3 cm(3), n = 18) or high (>or=3 cm(3), n = 16) T2 lesion load (LL). An Index of Brain Atrophy (IBA) was calculated and HMRS metabolite ratios were derived from a central brain area centred at the corpus callosum. RESULTS: Patient groups did not differ with regard to clinical characteristics and showed lower mean IBA and mean N-acetylaspartate:creatinine (NAA:Cr) ratios compared to healthy controls. CONCLUSION: PP patients with low and high brain T2LL have detectable brain atrophy and NAA:Cr reduction compared to healthy controls. In PP MS, T2 lesions alone are insufficient to explain the presence of brain atrophy and decrease in NAA:Cr.