Early detection of widespread progressive brain injury after cardiac arrest: a single case DTI and post-mortem histology study.

OBJECTIVE: We tested the hypothesis in sense of a proof of principle that white matter (WM) degeneration after cardiopulmonary arrest (CPA) can be assessed much earlier by diffusion tensor imaging (DTI) than by conventional MRI. METHODS: We performed DTI and T2-weighted FLAIR imaging over four serial acquisitions of a 76-year-old man with unresponsive wakefulness syndrome at day 41, 75, 173 and 284 after CPA. DTI was also performed in ten healthy control subjects. Fractional anisotropy (FA) derived from DTI was assessed in eleven regions of interest within the cerebral white matter (WM) and compared with post-mortem neuropathological findings. RESULTS: In contrast to conventional FLAIR images that revealed only circumscribed WM damage, the first DTI demonstrated significant reduction of FA across the whole WM. The following FLAIR images (MRI 2-4) revealed increasing atrophy and leukoaraiosis paralleled by clinical deterioration with reduction of wakefulness and intractable seizures. Neuropathological findings confirmed the widespread and marked brain injury following CPA. CONCLUSION: DTI may help to evaluate microstructural brain damage following CPA and may have predictive value for further evolution of cerebral degeneration in the chronic phase after CPA.

Voxel-based statistical analysis of fractional anisotropy and mean diffusivity in patients with unilateral temporal lobe epilepsy of unknown cause.

PURPOSE: To determine regional alterations of fractional anisotropy (FA) and mean diffusivity (MD) in patients with magnetic resonance imaging (MRI)-negative temporal lobe epilepsy with unknown cause (TLEu) using diffusion tensor imaging (DTI) and voxel-based statistics (VBS). METHODS: Ten patients with left TLEu and no abnormality on conventional MRI and 81 age-matched neurological healthy controls were studied. VBS analyses were used to compare FA and MD differences between patients and controls. All results were reported using stringent statistical thresholds corrected for multiple comparisons. RESULTS: Patients with TLEu had widespread and bilateral reduction of white matter FA, encompassing the temporal lobes, entire corpus callosum, thalamus, and other regions relative to controls. Increased MD was more spatially limited in patients, but was also observed in the thalamus. FA of the putamen was significantly increased bilaterally in patients relative to controls, which correlated with increasing macroscopic atrophy of the putamen. DISCUSSION: Water diffusion abnormalities are widespread and bilaterally distributed in patients with unilateral TLEu, which are beyond the resolution of conventional MRI. FA alterations are more widespread relative to MD alterations. This is the first study to show evidence of interrelated microscopic (ie, FA increase) and macroscopic (ie, atrophy) alterations of the putamen in patients with TLEu.

Concomitant fractional anisotropy and volumetric abnormalities in temporal lobe epilepsy: cross-sectional evidence for progressive neurologic injury.

BACKGROUND: In patients with temporal lobe epilepsy and associated hippocampal sclerosis (TLEhs) there are brain abnormalities extending beyond the presumed epileptogenic zone as revealed separately in conventional magnetic resonance imaging (MRI) and MR diffusion tensor imaging (DTI) studies. However, little is known about the relation between macroscopic atrophy (revealed by volumetric MRI) and microstructural degeneration (inferred by DTI). METHODOLOGY/PRINCIPAL FINDINGS: For 62 patients with unilateral TLEhs and 68 healthy controls, we determined volumes and mean fractional anisotropy (FA) of ipsilateral and contralateral brain structures from T1-weighted and DTI data, respectively. We report significant volume atrophy and FA alterations of temporal lobe, subcortical and callosal regions, which were more diffuse and bilateral in patients with left TLEhs relative to right TLEhs. We observed significant relationships between volume loss and mean FA, particularly of the thalamus and putamen bilaterally. When corrected for age, duration of epilepsy was significantly correlated with FA loss of an anatomically plausible route - including ipsilateral parahippocampal gyrus and temporal lobe white matter, the thalamus bilaterally, and posterior regions of the corpus callosum that contain temporal lobe fibres - that may be suggestive of progressive brain degeneration in response to recurrent seizures. CONCLUSIONS/SIGNIFICANCE: Chronic TLEhs is associated with interrelated DTI-derived and volume-derived brain degenerative abnormalities that are influenced by the duration of the disorder and the side of seizure onset. This work confirms previously contradictory findings by employing multi-modal imaging techniques in parallel in a large sample of patients.

Progression of microstructural putamen alterations in a case of symptomatic recurrent seizures using diffusion tensor imaging.

Microstructural alterations of the putamen were recently reported in patients with partial and generalized epilepsy disorders. However, it is unknown whether these alterations pre-exist or are secondary to recurrent seizures. Here we investigated the progression of putamen fractional anisotropy (FA) alterations in a case of recurrent psychomotor seizures using longitudinal diffusion tensor imaging (DTI) shortly before (DTI-1) and after a psychomotor seizure (DTI-2). We obtained FA values of a hypothesis-guided putamen region-of-interest (ROI) and seven exploratory ROIs. FA values from both DTIs were compared with reference values from 19 controls. Relative to controls, the patient's putamen FA was increased at DTI-1 (13% left putamen, 7% right putamen), an effect that was exacerbated at DTI-2 (24% left putamen (p<0.05), 20% right putamen). In the exploratory ROIs we found FA reductions in the corticospinal tract, temporal lobe, and occipital lobe (p<0.05) relative to controls at DTI-1 and DTI-2. In contrast to the putamen, all exploratory ROIs showed no relevant FA change between DTI-1 and DTI-2. These results suggest that recurrent seizures may lead to progressive microstructural putamen alterations.

Volume estimation of the thalamus using freesurfer and stereology: consistency between methods.

Freely available automated MR image analysis techniques are being increasingly used to investigate neuroanatomical abnormalities in patients with neurological disorders. It is important to assess the specificity and validity of automated measurements of structure volumes with respect to reliable manual methods that rely on human anatomical expertise. The thalamus is widely investigated in many neurological and neuropsychiatric disorders using MRI, but thalamic volumes are notoriously difficult to quantify given the poor between-tissue contrast at the thalamic gray-white matter interface. In the present study we investigated the reliability of automatically determined thalamic volume measurements obtained using FreeSurfer software with respect to a manual stereological technique on 3D T1-weighted MR images obtained from a 3 T MR system. Further to demonstrating impressive consistency between stereological and FreeSurfer volume estimates of the thalamus in healthy subjects and neurological patients, we demonstrate that the extent of agreeability between stereology and FreeSurfer is equal to the agreeability between two human anatomists estimating thalamic volume using stereological methods. Using patients with juvenile myoclonic epilepsy as a model for thalamic atrophy, we also show that both automated and manual methods provide very similar ratios of thalamic volume loss in patients. This work promotes the use of FreeSurfer for reliable estimation of global volume in healthy and diseased thalami.

Comparison of chromosomal aberrations in primary colorectal carcinomas to their pulmonary metastases.

Pulmonary metastases (PM) are frequent in colorectal carcinoma (CRC). However, little is known about the chromosomal imbalances in CRC that accompany metastatic pulmonary disease. We investigated tumor specimens of CRC (n=30) and their corresponding PM by comparative genomic hybridization (CGH). There were no substantial differences in the degree of chromosomal instability between CRC and PM, neither in average number of copy alterations (ANCA; 6.6 ± 0.8 and 7.7 ± 0.9) nor in gains (2.6 ± 0.5 and 2.6 ± 0.4), losses (3.6 ± 0.5 and 4.8 ± 0.6), or amplifications (0.4 ± 0.1 and 0.3 ± 0.1). Basically, similar patterns of chromosomal imbalances could be identified in both CRC and corresponding PM, most frequently including chromosomal gains at 7, 8q, 13q, and 20q, as well as losses at 4, 8p, 18q, and 20p. CRC and corresponding PM differed in frequencies for losses at chromosome arm 5q (3 vs. 26%; P=0.012). Losses at 4q and 11q in CRC were significantly associated with lower 5-year survival rates (80 vs. 24%, P=0.026 and 74 vs. 17%, P=0.007, respectively), and they may represent candidates for adverse prognostic markers in primary CRC.

High chromosomal instability in brain metastases of colorectal carcinoma.

Information on structural chromosomal changes in brain metastases (BM) of colorectal carcinoma (CRC) is very limited. Therapeutic and diagnostic strategies to reduce the risk of BM have potential impact on cancer mortality. By using comparative genomic hybridization, the primary CRC of 11 patients and their corresponding 13 BM were analyzed. BM showed significantly more mean chromosomal aberrations than the primary CRC (13.6+/-2.1 vs. 7.9+/-1.9, P=0.03), significantly more chromosomal gains (7.2+/-0.9 vs. 3.5+/-0.9, P=0.01), and tended to have also more losses (6.1+/-1.4 vs. 4.0+/-1.1, P=0.29). Changes that occurred significantly more often in BM than in primary CRC were gains of 8q, 12p, 12q, and 20p, as well as losses of 5q. BM of CRC show a significantly higher chromosomal instability in comparison to primary tumors. The prevalently altered genomic regions in the metastases of this study are likely to harbor genes that play an important role in the genesis of brain-specific metastasis.