Materials and Methods: Young (three women, three men; age range, 25–35 years) and elderly (four women, two men; age range, 68–72 years) groups underwent MR imaging and proton MR spectroscopic imaging at 3 T in this HIPAA-compliant prospective study and gave institutional review board–approved written consent. Volume of interest was centered on and tilted parallel to hippocampal anteroposterior plane. Absolute N-acetylaspartate (NAA), choline, and creatine levels were obtained in each voxel, with phantom replacement.

Results: Mean NAA, creatine, and choline concentrations in the young group were higher in posterior hippocampus (12.9 mmol/L ± 2.0 [standard deviation], 7.8 mmol/L ± 1.2, 2.3 mmol/L ± 0.4, respectively) than anterior hippocampus (8.0 mmol/L ± 1.1, 6.0 mmol/L ± 1.4, 1.5 mmol/L ± 0.2; P = .005, .02, and .0002, respectively). In the elderly group, mean concentrations were higher in posterior hippocampus (8.6 mmol/L ± 0.9, 5.6 mmol/L ± 0.6, 1.5 mmol/L ± 0.2, respectively) than anterior hippocampus (7.2 mmol/L ± 1.0, 2.4 mmol/L ± 0.3, 1.0 mmol/L ± 0.2; P = .006, .0001, .04, respectively). Mean concentrations were significantly higher in the young group (13.2 mmol/L ± 1.0, 7.4 mmol/L ± 0.8, 2.1 mmol/L ± 0.3, respectively) than in the elderly group (9.0 mmol/L ± 1.0, 5.8 mmol/L ± 0.8, 1.8 mmol/L ± 0.3; P = .0001, .01, .05, respectively). Posteroanterior metabolic gradients differed: NAA decreased faster in the young group (–1.0 mmol/L · cm^–1) than the elderly group (–0.7 mmol/L · cm^–1); creatine and choline concentrations decreased faster in the elderly group (–0.8 and –0.058 mmol/L · cm^–1, respectively) than the young group (–0.16 and –0.008 mmol/L · cm^–1, respectively). No left-right metabolic differences were found.

Conclusion: Significant metabolic heterogeneity was observed between groups and along anteroposterior axis of healthy hippocampus in both groups. Age matching and consistent voxel placement are important for correct comparisons of both absolute metabolic levels and metabolite ratios in longitudinal intra- and intersubject cross-sectional studies.

© RSNA, 2008

Materials and Methods: Ethics committee approval and informed consent were obtained. Twenty-four consecutive patients with symptomatic high-grade internal carotid artery stenosis (seven women; mean age, 73.1 years ± 9.4 [standard deviation]) were recruited from a prospective, randomized trial that compared carotid artery stent placement with endarterectomy. Magnetic resonance (MR) imaging, including CO₂ blood oxygen level–dependent (BOLD) MR, was performed 1–3 days before, 1–3 days after, and 1 month after carotid revascularization (carotid artery stent placement, n = 13; carotid endarterectomy, n = 11).

Results: Mean CVR in the ipsilateral middle cerebral artery (MCA) territory was reduced prior to treatment (mean T2* in ipsilateral territory, 1.92% ± 1.18; mean T2* in contralateral territory, 2.28% ± 1.15 [P < .05]) and normalized after treatment (mean T2* 1–3 days after treatment in ipsilateral territory, 2.66% ± 1.01; that in contralateral territory, 2.48% ± 1.27 [P > .05]; mean T2* 1 month after treatment in ipsilateral territory, 2.27% ± 1.05; that in contralateral territory, 2.14% ± 0.96 [P > .05]). Those patients who developed new periinterventional infarcts (n = 7 with punctate foci of restricted diffusion) had greater reduction of CVR in the ipsilateral MCA territory prior to treatment (relative reduction, 32.5% ± 46.0; P < .05) than those who did not develop infarction (n = 17; relative reduction, 9.2% ± 55.9).

Conclusion: CO₂ BOLD MR imaging could be used successfully to monitor the hemodynamic effects of carotid revascularization; initial reductions in CVR normalized after carotid revascularization. Severely reduced pretreatment CVR was associated with increased occurrence of new periinterventional therapy infarction.

© RSNA, 2008

Materials and Methods: Institutional review board approval and patient informed consent were obtained. Eleven patients undergoing carotid endarterectomy were examined with MR imaging of IPH, and MR images were assessed for T1 hyperintense intraplaque signal. A total of 160 images per patient were available for coregistration with corresponding histologic slices. Because of endarterectomy specimen size and degradation and processing artifacts, only 97 images were coregistered to corresponding histologic slices. A grid that consisted of 16 segments was overlaid on images for correlation of MR images and histologic slices. Only one of 16 segments was chosen randomly per slide and used in the analysis. Agreement between MR images and histologic slices was measured with the Cohen statistic.

Results: Strong agreement was seen between MR images and histologic slices, with T1-weighted high signal intensity corresponding to hemorrhagic material ( = 0.7–0.8). There was a low 2% false-negative rate for the detection of hemorrhage on the basis of T1-weighted hyperintensity (two of 97 measured segments). The results of diagnostic tests for T1 hyperintense detection of hemorrhage were as follows: sensitivity of 100%, specificity of 80%, positive predictive value of 70%, and negative predictive value of 100% for reader 1 and sensitivity of 94%, specificity of 88%, positive predictive value of 78%, and negative predictive value of 97% for reader 2.

Conclusion: With its high spatial resolution, MR imaging of IPH permits detection of plaque hemorrhage location, resulting in strong agreement between imaging and histologic findings.

© RSNA, 2008

Materials and Methods: Gene expression was determined for 52 newly diagnosed GBMs by using DNA microarrays, and the relationship to enhancement pattern and survival was analyzed. This study was approved by the institutional review board and was HIPAA compliant; informed consent was obtained.

Results: Thirty-eight percent (20 of 52) of GBMs were incompletely enhancing (IE). The expression of eight genes was increased more than twofold in IE GBM when compared with completely enhancing (CE) GBM. Among these were tight junction protein-2 (2.2-fold increase, P = .019), and the oligodendroglioma markers oligodendrocyte lineage transcription factor 2 (2.4-fold increase, P = .029) and Achaete-scute complex-like 1 (ASCL1; 2.7-fold increase, P = .023). The expression of 71 genes showed relative overexpression in CE when compared with IE GBM. These included several proangiogenic and edema-related genes, including vascular endothelial growth factor (2.1-fold, P = .005) and neuronal pentraxin-2 (3.0-fold, P = .029). Several genes associated with primary GBM were overexpressed in CE tumors, whereas ASCL1, which is associated with secondary GBM, was overexpressed in IE tumors. Many genes overexpressed in IE GBM were associated with longer survival, whereas several genes overexpressed in CE GBM correlated with shortened survival.

Conclusion: The enhancement pattern divides GBM in two groups with differing prognoses. By comparing gene expression between IE and CE GBMs, it was possible to identify genes that may affect magnetic resonance imaging features of edema and enhancement, and genes whose expression levels are predictive of both improved and shortened survival.

© RSNA, 2008

Materials and Methods: The institutional review board approved this HIPAA-compliant study, and the informed consent requirement was waived. Data from 39 patients (27 men, 12 women; age range, 19–78 years) who had histopathologically confirmed gliomas and who underwent surgery after preoperative functional MR imaging were analyzed. Fourteen patients had grade II or grade III gliomas, and 25 patients had grade IV gliomas. A change in BOLD SI was measured in motor cortices of tumor-containing and non–tumor-containing hemispheres. The effect of age and tumor grade, both individually and together, on BOLD functional MR SI was assessed with t tests and regression analysis.

Results: In patients with grade IV gliomas, SI change was lower in the tumor-containing hemisphere than in the non–tumor-containing hemisphere (P = .012). SI change decreased with increased age in the tumor-containing hemisphere in patients with grade II or III gliomas (P = .032) and in the non–tumor-containing hemisphere in patients with grade IV gliomas (P = .026). While advanced age and increased glioma grade reduced SI change, the combined effect of these factors was not additive. In patients with grade IV gliomas, tumor presence reduced SI change, but the level of reduction was uniform across all ages and did not correlate with age (P = .541).

Conclusion: In older patients with grade IV gliomas, BOLD SI is equivalent to that measured in younger patients with grade IV gliomas. Advanced age and tumor grade do not have a combined effect for reduction of BOLD SI. Rather, in patients with grade IV gliomas, tumor grade played a dominant role in reduction of SI change, whereas in patients with grade II and III gliomas, reduction of SI change correlated with only advanced age.

© RSNA, 2008

Materials and Methods: The study was approved by the local institutional review board; patients or their guardians provided informed consent. Magnetic resonance (MR) imaging was performed within 6 hours of symptom onset and again 1–11 days thereafter in 100 consecutive stroke patients, all of whom received intravenous thrombolytic therapy (mean age, 67 years). The MR imaging protocol included diffusion- and perfusion-weighted imaging for determination of apparent diffusion coefficient (ADC) and time to peak (TTP), along with quantitative T2 and T2* imaging. T2' maps were calculated and visually compared with ADC and TTP lesions by two independent observers.

Results: A T2'>ADC mismatch was observed by reader 1 in 73 (73%) of 100 patients, and by reader 2 in 65 (65%) patients. Respective sensitivities of T2'>ADC and of TTP>ADC mismatches for later infarct growth were 0.87 and 0.98 for reader 1 and 0.78 and 0.98 for reader 2, with respective specificities of 0.42 and 0.04 for reader 1 and 0.46 and 0.04 for reader 2. The odds ratios for infarct growth in the presence of a T2' > ADC mismatch were 4.59 (reader 1 P = .002) and 3.10 (reader 2 P = .012), while the odds ratios for TTP>ADC mismatch were 2.22 (reader 1 P = .606) and 1.73 (reader 2 P > .999).

Conclusion: The presence of a T2' > ADC mismatch is a more specific predictor of infarct growth than is TTP>ADC mismatch and hence may be of clinical value in patient selection for acute stroke therapies in the future.

© RSNA, 2008

Materials and Methods: The ethics committee approved the study, and patients gave written informed consent. Thirty-four consecutive patients (16 women, 18 men; mean age, 43.2 years) were included who met the following three criteria: They had a focal mass in or adjacent to eloquent cortex of the language or motor system, they had the ability to perform the functional MR imaging task, and they had to undergo surgery with intraoperative ECM. Functional MR imaging with verb generation (n = 17) or finger tapping of the contralateral hand (n = 17) was performed at 1.5 T with a block design and an echo-planar gradient-echo T2*-weighted sequence. Cortex essential for language or hand motor functions was mapped with ECM. A site-by-site comparison between functional MR imaging and ECM was performed with the aid of a neuronavigational device. Sensitivity and specificity were calculated according to task performed, histopathologic findings, and tumor grade. Exact 95% confidence intervals were calculated for each sensitivity and specificity value.

Results: For 34 consecutive patients, there were 28 with gliomas, two with metastases, one with meningioma, and three with cavernous angiomas. A total of 251 cortical sites were tested with ECM; overall functional MR imaging sensitivity and specificity were 83% and 82%, respectively. Sensitivity (65%) was lower and specificity (93%) was higher in World Health Organization grade IV gliomas compared with grade II (sensitivity, 93%; specificity, 79%) and III (sensitivity, 93%; specificity, 76%) gliomas. At 3 months after surgery, language proficiency was unchanged in 15 patients; functionality of the contralateral arm was unchanged in 14 patients and improved in one patient.

Conclusion: Functional MR imaging is a sensitive and specific method for mapping language and motor functions.

© RSNA, 2008

Materials and Methods: This study was IRB approved; written informed consent was obtained; and included 65 AD patients (38 women, 27 men; age, 52–81 years), 45 MCI patients (22 women, 23 men; age, 56–80 years), 27 patients with subjective complaints (12 women, 15 men; age, 50–87 years), and 10 healthy controls (six women, four men; age, 53–80 years). Two magnetic resonance (MR) images were acquired at average interval of 1.8 years ± 0.7 (standard deviation). Baseline brain volume and whole-brain atrophy rates were measured on three-dimensional T1-weighted MR images (1.0 T; single slab, 168 sections; matrix size, 256 x 256; field of view, 250 mm; voxel size, 1 x 1 x 1.5 mm; repetition time msec/echo time msec/inversion time msec, 15/7/300; and flip angle, 15°). Associations were assessed by using partial-correlations. Cox proportional hazards models were used to estimate risk of developing dementia.

Results: Baseline brain volume was lowest in AD but did not differ significantly between MCI, subjective complaints, and control groups (P > .38). Whole-brain atrophy rates were higher in AD (–1.9% per year ± 0.9) than MCI (–1.2% per year ± 0.9, P = .003) patients, who had higher whole-brain atrophy rates than patients with subjective complaints (–0.7% per year ± 0.7, P = .03) and controls (–0.5% per year ± 0.5, P = .05). Whole-brain atrophy rate correlated with annualized Mini-Mental State Examination (MMSE) change (r = 0.48, P < .001), while baseline volume did not (r = 0.11, P = .22). Cox models showed that—after correction for age, sex, and baseline MMSE—a higher whole-brain atrophy rate was associated with an increased risk of progression to dementia (highest vs lowest tertile [hazard ratio, 3.6; 95% confidence interval: 1.2, 11.4]).

Conclusion: Whole-brain atrophy rate was strongly associated with cognitive decline. In nondemented participants, a high whole-brain atrophy rate was associated with an increased risk of progression to dementia.

© RSNA, 2008

Materials and Methods: The regional ethics committee approved the study and written informed consent was obtained from all participants. The study included 25 patients with AD (11 men, 14 women; mean age ± standard deviation [SD], 73 years ± 6; Mini-Mental State Examination (MMSE) score, 24.4 ± 2.7), 24 patients with amnestic MCI (10 men, 14 women; mean age ± SD, 74 years ± 8; MMSE score, 27.2 ± 1.4) and 25 elderly healthy controls (13 men, 12 women; mean age ± SD, 64 years ± 8). For each participant, the hippocampi were automatically segmented on three-dimensional T1-weighted magnetic resonance (MR) images with high spatial resolution. Segmentation was performed by using recently developed software that allows fast segmentation with minimal user input. Group differences in hippocampal volume were assessed by using Student t tests. To obtain robust estimates of P values, the correct classification rate, sensitivity, and specificity, bootstrap methods were used.

Results: Significant hippocampal volume reductions were detected in all groups of patients (–32% in AD patients vs controls, P < .001; –19% in MCI patients vs controls, P < .001; and –15% in AD patients vs MCI patients, P < .01). Individual classification on the basis of hippocampal volume resulted in 84% correct classification (sensitivity, 84%; specificity, 84%) between AD patients and controls and 73% correct classification (sensitivity, 75%; specificity, 70%) between MCI patients and controls.

Conclusion: This automated method can serve as an alternative to manual tracing and may thus prove useful in assisting with the diagnosis of AD.

© RSNA, 2008

Materials and Methods: All patients gave written informed consent for the initial magnetic resonance (MR) studies, and the institutional review board and local research ethics committee waived initial informed consent for the pooled analysis. A total of 190 patients with symptomatic carotid artery disease underwent fluid-attenuated inversion-recovery imaging of the brain and fat-suppressed black-blood T1-weighted MR imaging of the carotid arteries. The volumes of periventricular lesions, subcortical lesions, and total WMHLs were calculated and compared between hemispheres in relation to symptoms and IPH, and their interaction was calculated and compared by using repeated measures three-factorial multivariate analysis.

Results: After exclusion of 12 patients, 178 patients (116 men, 62 women; mean age, 70.2 years ± 8.6 [standard deviation]) remained. There was no significant difference in WMHL volume between the symptomatic and asymptomatic hemispheres, and WMHL volume was not related to the degree of carotid stenosis. The presence of carotid IPH significantly interacted with the interhemispheric WMHL difference (Wilks test, F = 9.95; df = 3; P < .001). Univariate analysis showed larger total and periventricular WMHL volumes (P < .05) in patients with ipsilateral IPH.

Conclusion: Carotid artery disease and leukoaraiosis were associated with features that indicated plaque instability, namely IPH, whereas the degree of stenosis had no effect.

© RSNA, 2008

Materials and Methods: This study was approved by the institutional review board and was compliant with HIPAA regulations. Informed consent was obtained from each subject. The authors identified 54 subjects who underwent antemortem ¹H MR spectroscopy and were clinically healthy or had AD-type pathology with low to high likelihood of AD according to National Institute on Aging–Reagan neuropathologic criteria at autopsy. They investigated the associations between ¹H MR spectroscopy metabolite measurements and Braak neurofibrillary tangle stage (Braak stage), neuritic plaque score, and AD likelihood, with adjustments for subject age, subject sex, and time between ¹H MR spectroscopy and death.

Results: Decreases in N-acetylaspartate–to-creatine ratio, an index of neuronal integrity, and increases in myo-inositol–to-creatine ratio were associated with higher Braak stage, higher neuritic plaque score, and greater likelihood of AD. The N-acetylaspartate–to–myo-inositol ratio proved to be the strongest predictor of the pathologic likelihood of AD. The strongest association observed was that between N-acetylaspartate–to–myo-inositol ratio and Braak stage (R_N² = 0.47, P < .001).

Conclusion: Antemortem ¹H MR spectroscopy metabolite changes correlated with AD-type pathology seen at autopsy. The study findings validated ¹H MR spectroscopy metabolite measurements against the neuropathologic criteria for AD, and when combined with prior longitudinal ¹H MR spectroscopy findings, indicate that these measurements could be used as biomarkers for disease progression in clinical trials.

© RSNA, 2008