Comprehensive Update and Review of Clinical and Imaging Features of SMART Syndrome.

Stroke-like migraine attacks after radiation therapy (SMART) syndrome is a delayed complication of cranial irradiation, with subacute onset of stroke-like symptoms including seizures, visual disturbance, speech impairment, unilateral hemianopsia, facial droop, and aphasia, often associated with migraine-type headache. The diagnostic criteria were initially proposed in 2006. However, the diagnosis of SMART syndrome is challenging because clinical symptoms and imaging features of SMART syndrome are indeterminate and overlap with tumor recurrence and other neurologic diseases, which may result in inappropriate clinical management and unnecessary invasive diagnostic procedures. Recently, various imaging features and treatment recommendations for SMART syndrome have been reported. Radiologists and clinicians should be familiar with updates on clinical and imaging features of this delayed radiation complication because recognition of this entity can facilitate proper clinical work-up and management. This review provides current updates and a comprehensive overview of the clinical and imaging features of SMART syndrome.

Differentiation of Skull Base Chondrosarcomas, Chordomas, and Metastases: Utility of DWI and Dynamic Contrast-Enhanced Perfusion MR Imaging.

BACKGROUND AND PURPOSE: Differentiation of skull base tumors, including chondrosarcomas, chordomas, and metastases, on conventional imaging remains a challenge. We aimed to test the utility of DWI and dynamic contrast-enhanced MR imaging for skull base tumors. MATERIALS AND METHODS: Fifty-nine patients with chondrosarcomas, chordomas, or metastases between January 2015 and October 2021 were included in this retrospective study. Pretreatment normalized mean ADC and dynamic contrast-enhanced MR imaging parameters were calculated. The Kruskal-Wallis H test for all tumor types and the Mann-Whitney U test for each pair of tumors were used. RESULTS: Fifteen chondrosarcomas (9 men; median age, 62 years), 14 chordomas (6 men; median age, 47 years), and 30 metastases (11 men; median age, 61 years) were included in this study. Fractional plasma volume helped distinguish all 3 tumor types (P = .003, <.001, and <.001, respectively), whereas the normalized mean ADC was useful in distinguishing chondrosarcomas from chordomas and metastases (P < .001 and P < .001, respectively); fractional volume of extracellular space, in distinguishing chondrosarcomas from metastases (P = .02); and forward volume transfer constant, in distinguishing metastases from chondrosarcomas/chondroma (P = .002 and .002, respectively) using the Kruskal-Wallis H test. The diagnostic performances of fractional plasma volume for each pair of tumors showed areas under curve of 0.86-0.99 (95% CI, 0.70-1.0); the forward volume transfer constant differentiated metastases from chondrosarcomas/chordomas with areas under curve of 0.82 and 0.82 (95% CI, 0.67-0.98), respectively; and the normalized mean ADC distinguished chondrosarcomas from chordomas/metastases with areas under curve of 0.96 and 0.95 (95% CI, 0.88-1.0), respectively. CONCLUSIONS: DWI and dynamic contrast-enhanced MR imaging sequences can be beneficial for differentiating the 3 common skull base tumors.

Prognostic Factors of Stroke-Like Migraine Attacks after Radiation Therapy (SMART) Syndrome.

BACKGROUND AND PURPOSE: Prognostic factors of stroke-like migraine attacks after radiation therapy (SMART) syndrome have not been fully explored. This study aimed to assess clinical and imaging features to predict the clinical outcome of SMART syndrome. MATERIALS AND METHODS: We retrospectively reviewed the clinical manifestations and imaging findings of 20 patients with SMART syndrome (median age, 48 years; 5 women) from January 2016 to January 2020 at 4 medical centers. Patient demographics and MR imaging features at the time of diagnosis were reviewed. This cohort was divided into 2 groups based on the degree of clinical improvement (completely versus incompletely recovered). The numeric and categoric variables were compared as appropriate. RESULTS: There were statistically significant differences between the completely recovered group (n = 11; median age, 44 years; 2 women) and the incompletely recovered group (n = 9; median age, 55 years; 3 women) in age, months of follow-up, and the presence of steroid treatment at diagnosis (P = .028, .002, and .01, respectively). Regarding MR imaging features, there were statistically significant differences in the presence of linear subcortical WM susceptibility abnormality, restricted diffusion, and subcortical WM edematous changes in the acute SMART region (3/11 versus 8/9, P = .01; 0/11 versus 4/9, P = .026; and 2/11 versus 7/9, P = .022, respectively). Follow-up MRIs showed persistent susceptibility abnormality (11/11) and subcortical WM edematous changes (9/9), with resolution of restricted diffusion (4/4). CONCLUSIONS: Age, use of steroid treatment at the diagnosis of SMART syndrome, and MR imaging findings of abnormal susceptibility signal, restricted diffusion, and subcortical WM change in the acute SMART region can be prognostic factors in SMART syndrome.

Diagnostic Role of Diffusion-Weighted and Dynamic Contrast-Enhanced Perfusion MR Imaging in Paragangliomas and Schwannomas in the Head and Neck.

BACKGROUND AND PURPOSE: Distinguishing schwannomas from paragangliomas in the head and neck and determining succinate dehydrogenase (SDH) mutation status in paragangliomas are clinically important. We aimed to assess the clinical usefulness of DWI and dynamic contrast-enhanced MR imaging in differentiating these 2 types of tumors, as well as the SDH mutation status of paragangliomas. MATERIALS AND METHODS: This retrospective study from June 2016 to June 2020 included 42 patients with 15 schwannomas and 27 paragangliomas (10 SDH mutation-positive and 17 SDH mutation-negative). ADC values, dynamic contrast-enhanced MRI parameters, and tumor imaging characteristics were compared between the 2 tumors and between the mutation statuses of paragangliomas as appropriate. Multivariate stepwise logistic regression analysis was performed to identify significant differences in these parameters. RESULTS: Fractional plasma volume (P ≤ .001), rate transfer constant (P = .038), time-to-maximum enhancement (P < .001), maximum signal-enhancement ratio (P < .001) and maximum concentration of contrast agent (P < .001), velocity of enhancement (P = .002), and tumor characteristics including the presence of flow voids (P = .001) and enhancement patterns (P = .027) showed significant differences between schwannomas and paragangliomas, though there was no significant difference in ADC values. In the multivariate logistic regression analysis, fractional plasma volume was identified as the most significant value for differentiation of the 2 tumor types (P = .014). ADC values were significantly higher in nonhereditary than in hereditary paragangliomas, while there was no difference in dynamic contrast-enhanced MR imaging parameters. CONCLUSIONS: Dynamic contrast-enhanced MR imaging parameters show promise in differentiating head and neck schwannomas and paragangliomas, while DWI can be useful in detecting SDH mutation status in paragangliomas.

Cerebrovascular manifestations in neurosarcoidosis: how common are they and does perivascular enhancement matter?

AIM: To determine the occurrence of ischaemic and haemorrhagic events in patients with neurosarcoidosis at presentation and follow-up and to evaluate its association with perivascular enhancement. MATERIALS AND METHODS: The MRI findings in patients with neurosarcoidosis who presented to our institute from 2002-2017 were retrospectively reviewed, with emphasis on cerebrovascular events. A chi-squared test was used to evaluate the statistical association with presence of perivascular enhancement. RESULTS: A total of 49 patients (32 females and 17 males) were analysed. Ischaemic events were noted in four patients at presentation while parenchymal haemorrhages occurred in three patients. The combined occurrence of cerebrovascular events (CVEs) at presentation was 14%. On follow-up, three additional patients developed ischaemic infarcts, of which, one patient had parenchymal haemorrhage at presentation. Additionally, one patient also developed new parenchymal haemorrhages. In total, 10 patients in current cohort developed CVEs, either at presentation or on follow-up. Perivascular enhancement was seen in 50% of patients with cerebrovascular events and 18% of patients with neurosarcoidosis, but no CVEs. This was statistically significant (p<0.05). CONCLUSION: CVEs in patients with neurosarcoidosis are more common than previously reported and appear to be significantly related to the presence of perivascular enhancement on imaging.

Role of the Apparent Diffusion Coefficient as a Predictor of Tumor Progression in Patients with Chordoma.

BACKGROUND AND PURPOSE: Diffusion-weighted imaging may aid in distinguishing aggressive chordoma from nonaggressive chordoma. This study explores the prognostic role of the apparent diffusion coefficient in chordomas. MATERIALS AND METHODS: Sixteen patients with residual or recurrent chordoma were divided postoperatively into those with an aggressive tumor, defined as a growing tumor having a doubling time of <1 year, and those with a nonaggressive tumor on follow-up MR images. The ability of the ADC to predict an aggressive tumor phenotype was investigated by receiver operating characteristic analysis. The prognostic role of ADC was assessed using a Kaplan-Meier curve with a log-rank test. RESULTS: Seven patients died during a median follow-up of 48 months (range, 4-126 months). Five of these 7 patients were in the aggressive tumor group, and 2 were in the nonaggressive tumor group. The mean ADC was significantly lower in the aggressive tumor group than in the nonaggressive tumor group (P = .002). Receiver operating characteristic analysis showed that a cutoff ADC value of 1.494 × 10-3 × mm2/s could be used to diagnose aggressive tumors with an area under the curve of 0.983 (95% CI, 0.911-1.000), a sensitivity of 1.000 (95% CI, 0.541-1.000), and a specificity of 0.900 (95% CI, 0.555-0.998). Furthermore, a cutoff ADC of ≤1.494 × 10-3 × mm2/s was associated with a significantly worse prognosis (P = .006). CONCLUSIONS: Lower ADC values could predict tumor progression in postoperative chordomas.

Atypical Presentations of Intracranial Hypotension: Comparison with Classic Spontaneous Intracranial Hypotension.

BACKGROUND AND PURPOSE: Atypical clinical presentations of spontaneous intracranial hypotension include obtundation, memory deficits, dementia with frontotemporal features, parkinsonism, and ataxia. The purpose of this study was to compare clinical and imaging features of spontaneous intracranial hypotension with typical-versus-atypical presentations. MATERIALS AND METHODS: Clinical records and neuroimaging of patients with spontaneous intracranial hypotension from September 2005 to August 2014 were retrospectively evaluated. Patients with classic spontaneous intracranial hypotension (n = 33; mean age, 41.7 ± 14.3 years) were compared with those with intracranial hypotension with atypical clinical presentation (n = 8; mean age, 55.9 ± 14.1 years) and 36 controls (mean age, 41.4 ± 11.2 years). RESULTS: Patients with atypical spontaneous intracranial hypotension were older than those with classic spontaneous intracranial hypotension (55.9 ± 14.1 years versus 41.7 ± 14.3 years; P = .018). Symptom duration was shorter in classic compared with atypical spontaneous intracranial hypotension (3.78 ± 7.18 months versus 21.93 ± 18.43 months; P = .015). There was no significant difference in dural enhancement, subdural hematomas, or cerebellar tonsil herniation. Patients with atypical spontaneous intracranial hypotension had significantly more elongated anteroposterior midbrain diameter compared with those with classic spontaneous intracranial hypotension (33.6 ± 2.9 mm versus 27.3 ± 2.9 mm; P < .001) and shortened pontomammillary distance (2.8 ± 1 mm versus 5.15 ± 1.5 mm; P < .001). Patients with atypical spontaneous intracranial hypotension were less likely to become symptom-free, regardless of treatment, compared with those with classic spontaneous intracranial hypotension (χ(2) = 13.99, P < .001). CONCLUSIONS: In this sample of 8 patients, atypical spontaneous intracranial hypotension was a more chronic syndrome compared with classic spontaneous intracranial hypotension, with more severe brain sagging, lower rates of clinical response, and frequent relapses. Awareness of atypical presentations of spontaneous intracranial hypotension is paramount.

Limbic Tumors of the Temporal Lobe: Radiologic-Pathologic Correlation.

PURPOSE: The purpose of this study was to assess imaging and pathologic characteristics of limbic tumors. Our hypothesis was that temporal lobe limbic tumors have distinctive features from extralimbic tumors. METHODS: This retrospective radiologic-pathologic correlation study of primary temporal lobe tumors (excluding glioblastoma) distinguished limbic from extralimbic tumors based on preoperative magnetic resonance imaging. Limbic tumors were categorized according to Yasargil's classification into (1) mediobasal temporal (mbT), (2) insular-temporo-opercular (I-TO), and (3) fronto-orbital-insular-temporopolar (FO-I-TP). RESULTS: A total of 50 cases with a mean age at diagnosis of 38 ± 19.9 years (14 women, 36 men) were included. Pathologic diagnoses were as follows: 20 anaplastic astrocytomas, 11 gangliogliomas, 8 astrocytomas (World Health Organization grade II), 3 pilocytic astrocytomas, 2 dysembryoplastic neuroepithelial tumors, 2 oligodendrogliomas (grade II), 2 anaplastic oligodendrogliomas, 1 low-grade glioneuronal tumor, and 1 atypical extraventricular neurocytoma. In all, 36 tumors were limbic and displayed consistent growth patterns (16 mbT, 11 I-TO, 8 FO-I-TP, and 1 pantemporal) and 14 were extralimbic. There were no differences between limbic and extralimbic tumors with regard to age, sex, pathologic diagnosis, and presentation with seizures. mbT tumors had more frequent neuronal differentiation (50 %) than I-TO (0 %) and FO-I-TP (25 %) tumors (chi-square = 7.8, df = 2, p = 0.02). Neuronal differentiation correlated with lower grade (r = 0.52, p < 0.01) and younger age (r = 0.52, p < 0.01). CONCLUSIONS: Limbic tumors displayed consistent growth routes. mbT limbic tumors had more frequent neuronal differentiation, which may result from proximity to the neurogenic subgranular zone of the hippocampus. Neuronal differentiation was maximal in mbT and lowest in I-TO and FO-I-TP tumors and correlated with lower tumor grade and younger age at diagnosis.

Pyogenic and non-pyogenic spinal infections: emphasis on diffusion-weighted imaging for the detection of abscesses and pus collections.

The incidence of spinal infections has increased in the past two decades, owing to the increasing number of elderly patients, immunocompromised conditions, spinal surgery and instrumentation, vascular access and intravenous drug use. Conventional MRI is the gold standard for diagnostic imaging; however, there are still a significant number of misdiagnosed cases. Diffusion-weighted imaging (DWI) with a b-value of 1000 and apparent diffusion coefficient (ADC) maps provide early and accurate detection of abscess and pus collection. Pyogenic infections are classified into four types of extension based on MRI and DWI findings: (1) epidural/paraspinal abscess with spondylodiscitis, (2) epidural/paraspinal abscess with facet joint infection, (3) epidural/paraspinal abscess without concomitant spondylodiscitis or facet joint infection and (4) intradural abscess (subdural abscess, purulent meningitis and spinal cord abscess). DWI easily detects abscesses and demonstrates the extension, multiplicity and remote disseminated infection. DWI is often a key image in the differential diagnosis. Important differential diagnoses include epidural, subdural or subarachnoid haemorrhage, cerebrospinal fluid leak, disc herniation, synovial cyst, granulation tissue, intra- or extradural tumour and post-surgical fluid collections. DWI and the ADC values are affected by susceptibility artefacts, incomplete fat suppression and volume-averaging artefacts. Recognition of artefacts is essential when interpreting DWI of spinal and paraspinal infections. DWI is not only useful for the diagnosis but also for the treatment planning of pyogenic and non-pyogenic spinal infections.

Reduced medial temporal lobe N-acetylaspartate in cognitively impaired but nondemented patients.

BACKGROUND: N-acetylaspartate (NAA) in the medial temporal lobe (MTL) and parietal lobe gray matter (GM) is diminished in Alzheimer disease (AD). Because NAA is considered a marker of neuronal integrity, reduced medial temporal and parietal lobe NAA could be an early indication of dementia-related pathology in elderly individuals. OBJECTIVES: 1) To determine whether cognitively impaired but nondemented (CIND) elderly individuals exhibit a similar pattern of reduced medial temporal and parietal lobe NAA as AD patients. 2) To compare regional NAA patterns, hippocampal and neocortical gray matter (GM) volumes in CIND patients who remained cognitively stable and those who became demented over 3.6 years of follow-up. 3) To examine the relationship between memory performance, medial temporal lobe NAA, and hippocampal volume. METHODS: Seventeen CIND, 24 AD, and 24 cognitively normal subjects were studied using MRSI and MRI. RESULTS: Relative to controls, CIND patients had reduced MTL NAA (19 to 21%, p = 0.005), hippocampal (11 to 14%, p < or = 0.04), and neocortical GM (5%, p = 0.05) volumes. CIND patients who later became demented had less MTL NAA (26%, p = 0.01), hippocampal (17 to 23%, p < or = 0.05), and neocortical GM (13%, p = 0.02) volumes than controls, but there were no significant differences between stable CIND patients and controls. MTL NAA in combination with hippocampal volume improved discrimination of CIND and controls over hippocampal volume alone. In AD and CIND patients, decreased MTL NAA correlated significantly with impaired memory performance. CONCLUSION: Reduced medial temporal lobe N-acetylaspartate, together with reduced hippocampal and neocortical gray matter volumes, may be early indications of dementia-related pathology in subjects at high risk for developing dementia.

White matter hyperintensities are significantly associated with cortical atrophy in Alzheimer's disease.

BACKGROUND AND OBJECTIVE: Methodological variability in the assessment of white matter hyperintensities (WMH) in dementia may explain inconsistent reports of its prevalence and impact on cognition. We used a method of brain MRI segmentation for quantifying both tissue and WMH volumes in Alzheimer's disease (AD) and examined the association between WMH and structural and cognitive variables. METHODS: A consecutive series of 81 patients meeting NINCDS-ADRDA criteria for probable AD was studied. Nineteen healthy volunteers of comparable age served as the control group. Patients had a complete neurological and neuropsychological evaluation, and a three dimensional MRI was obtained. Images were segmented into grey matter, white matter, and cerebrospinal fluid. WMH were edited on segmented images, and lobar assignments were based on Talairach coordinates. RESULTS: Mild and moderate to severe AD patients had significantly more WMH than controls (p<0.05). WMH preferentially involved the frontal lobes (70%), were inversely correlated with grey matter cortical volume (R(2) = 0.23, p<0.001), and were significantly associated with vascular risk factors and with a worse performance on memory tasks. CONCLUSION: Objective measurements of tissue volumes in AD demonstrated that WMH are significantly related to cortical atrophy and neuropsychological impairment.

Different patterns of N-acetylaspartate loss in subcortical ischemic vascular dementia and AD.

OBJECTIVES: 1) To determine the regional pattern of reduced N-acetylaspartate (NAA) in subcortical ischemic vascular dementia (SIVD); 2) to explore the relationship between NAA reduction and subcortical vascular disease; and 3) to test if MR spectroscopic imaging (MRSI) in combination with structural MRI improves differentiation between SIVD and Alzheimer disease (AD). METHODS: Thirteen patients with SIVD (71 +/- 8 years old) and 43 patients with AD of comparable age and dementia severity were studied using MRSI and MRI. Patients were compared to 52 cognitively normal subjects with and without lacunes. RESULTS: Compared to controls, patients with SIVD had lower NAA by 18% (p < 0.001) in frontal cortex and by 27% (p < 0.003) in parietal cortex, but no significant NAA reduction in white matter and medial temporal lobe. Compared to patients with AD, patients with SIVD had lower NAA by 13% (p < 0.02) in frontal cortex and by 20% (p < 0.002) in left parietal cortex. Cortical NAA decreased in SIVD with increasing white matter lesions (r = 0.54, p < 0.02) and number of lacunes (r = 0.59, p < 0.02). Thalamic lacunes were associated with greater NAA reduction in frontal cortex than were lacunes outside the thalamus (p < 0.02) across groups, after adjusting for cognitive impairments. Adding parietal NAA to MRI-derived hippocampal atrophy improved separation between SIVD and AD (p = 0.02) from 79 to 89%. CONCLUSIONS: These results emphasize the importance of cortical dysfunction as a factor in SIVD and indicate a characteristic pattern of metabolite change that might serve as a basis for improved diagnosis.

Selective reduction of N-acetylaspartate in medial temporal and parietal lobes in AD.

BACKGROUND: Both AD and normal aging cause brain atrophy, limiting the ability of MRI to distinguish between AD and age-related brain tissue loss. MRS imaging (MRSI) measures the neuronal marker N-acetylaspartate (NAA), which could help assess brain change in AD and aging. OBJECTIVES: To determine the effects of AD on concentrations of NAA, and choline- and creatine-containing compounds in different brain regions and to assess the extent NAA in combination with volume measurements by MRI improves discrimination between AD patients and cognitively normal subjects. METHODS: Fifty-six patients with AD (mean age: 75.6 +/- 8.0 years) and 54 cognitively normal subjects (mean age: 74.3 +/- 8.1 years) were studied using MRSI and MRI. RESULTS: NAA concentration was less in patients with AD compared with healthy subjects by 21% (p < 0.0001) in the medial temporal lobe and by 13% to 18% (p < 0.003) in parietal lobe gray matter (GM), but was not changed significantly in white matter and frontal lobe GM. In addition to lower NAA, AD patients had 29% smaller hippocampi and 11% less cortical GM than healthy subjects. Classification of AD and healthy subjects increased significantly from 89% accuracy using hippocampal volume alone to 95% accuracy using hippocampal volume and NAA together. CONCLUSION: In addition to brain atrophy, NAA reductions occur in regions that are predominantly impacted by AD pathology.

1H MRSI predicts surgical outcome in MRI-negative temporal lobe epilepsy.

1H MRS imaging (MRSI) was performed on 15 patients with MRI-negative temporal lobe epilepsy (TLE) who underwent seizure surgery. The non-seizure-free patients (NSF) ipsilateral hippocampal N-acetylaspartate (NAA)/(Cr+Cho) z scores were lower than the contralateral scores (p = 0.04), and the NSF ipsilateral z scores were lower than the seizure-free patients' (SF) ipsilateral z scores (p = 0.0049). Similarly, NSF contralateral scores were lower than contralateral SF (p = 0.02). These findings suggest NAA predicts the surgical outcome in patients with TLE without evidence of mesial temporal sclerosis on MRI.

Region and tissue differences of metabolites in normally aged brain using multislice 1H magnetic resonance spectroscopic imaging.

Quantitative measurements of regional and tissue specific concentrations of brain metabolites were measured in elderly subjects using multislice proton magnetic resonance spectroscopic imaging ((1)H MRSI). Selective k-space extrapolation and an inversion-recovery sequence were used to minimize lipid contamination and linear regression was used to account for partial volume problems. The technique was applied to measure the concentrations of N-acetyl aspartate (NAA), and creatine (Cr)- and choline (Cho)-containing compounds in cortical gray and white matter, and white matter lesions of the frontal and the parietal lobe in 40 normal elderly subjects (22 females and 18 males, 56-89 years old, mean age 74 +/- 8). NAA was about 15% lower in cortical gray matter and 23% lower in white matter lesions when compared to normal white matter. Cr was 11% higher in cortical gray matter than in white matter, and also about 15% higher in the parietal cortex than in the frontal cortex. Cho was 28% lower in cortical gray matter than in white matter. Furthermore, NAA and Cr changes correlated with age. In conclusion, regional and tissue differences of brain metabolites must be considered in addition to age-related changes when interpreting (1)H MRSI data.

Temporal lobe epilepsy: qualitative reading of 1H MR spectroscopic images for presurgical evaluation.

PURPOSE: To study the feasibility and clinical potential of visual inspection of hydrogen 1 magnetic resonance (MR) spectroscopic metabolite images for the lateralization of unilateral nonlesional temporal lobe epilepsy (TLE). MATERIALS AND METHODS: MR imaging and 1H MR spectroscopic imaging were performed of the temporal lobes in 50 patients with TLE and 23 age-matched healthy volunteers. N-acetylaspartate (NAA) and creatine plus choline metabolite images were read by two neuroradiologists who determined lateralization according to the side of lower NAA signal intensity. Quantitative estimates of NAA were calculated by using an automated fitting program. RESULTS: Agreement in lateralization between readers was significant with a kappa score of 0.53 for all patients with TLE and 0.63 for patients displaying mild or marked NAA asymmetry. Among the 50 patients with TLE, lateralization was determined correctly by reader 1 in 38 (76%) patients and by reader 2 in 31 (62%) patients. If limited to patients with mild or marked NAA asymmetry, correct lateralization improved to 30 (77%) of 39 and 16 (80%) of 20 patients, respectively. Combined qualitative reading and quantitative spectral fitting enabled lateralization in 34 (85%) of 40 patients with TLE for reader 1 and 30 (77%) of 39 for reader 2, including nine of 14 patients with TLE with negative MR images. CONCLUSION: Reading of metabolite images is a feasible and fast means for noninvasive evaluation of patients with TLE who are candidates for surgery and enables lateralization in some patients with negative MR images.

1H MRSI comparison of white matter and lesions in primary progressive and relapsing-remitting MS.

OBJECTIVE: To compare brain metabolite levels in patients with primary progressive (PP) and relapsing remitting (RR) MS and controls. HYPOTHESES: (1) creatine (Cr), a putative marker of gliosis, is elevated and N-acetylaspartate (NAA), a putative marker of axonal density and functional integrity, is reduced in PPMS lesions and normal appearing white matter (NAWM) compared to control white matter; (2) The pattern of metabolite change in PPMS is different than in RRMS. METHODS: MRI and proton magnetic resonance spectroscopic imaging (1H MRSI) were collected from 15 PPMS patients, 13 RRMS patients, and 20 controls. RESULTS: Cr was increased in PPMS NAWM compared to controls (P=0.035), and compared to RRMS NAWM (P=0.038). Cr was increased in focal MRI lesions from PPMS compared to lesions from RRMS (P=0.044) and compared to control white matter (P=0.041). NAA was similarly reduced in PPMS and RRMS NAWM compared to control. NAA was similarly reduced in PPMS and RRMS lesions, compared to control white matter. CONCLUSIONS: Creatine is higher in PPMS than RRMS NAWM and focal lesions. This observation is consistent with the notion that progressive disability in PPMS reflects increased gliosis and axonal loss whereas disability in RRMS reflects the cumulative effects of acute inflammatory lesions and axonal loss.

Administration and (1)H MRS detection of histidine in human brain: application to in vivo pH measurement.

Measurement of histidine in vivo offers the potential for tissue pH measurement using routinely performed (1)H MR spectroscopy. In the brain, however, histidine concentrations are generally too low for reliable measurement. By using oral loading of histidine, this study demonstrates that brain concentrations can be significantly increased, enabling detection of histidine by localized (1)H MR measurements and making in vivo pH measurement possible. In studies carried out on healthy human subjects at 1.5 T, a consistent spectral quality downfield from water was achieved using a PRESS sequence at short echo times. Measurements at different TE values helped to characterize the downfield spectral region. Histidine loading of 400 mg/kg of body weight increased brain histidine levels by approximately 0.8 mM, with maximum histidine concentration reached 4 to 7 hr after consumption. The pH calculated from histidine resonances was 6.96, and a hyperventilation study demonstrated the potential for measuring altered pH.