Postmortem unfixed whole brains from five multiple sclerosis (MS) patients were examined by MRI using a T2- and T1-weighted spin-echo (SE) sequence and histology to investigate the histopathologic characteristics of hypointense lesions on T1-weighted SE MR images. The degree of hypointensity was scored semiquantitatively by two blinded observers in reference to normal-appearing white matter. Signal intensities of the lesions and the normal-appearing white matter were measured to obtain contrast ratios. Hematoxylin-eosin stain was used to assess degree of matrix destruction (decrease of density of the neuropil) and cellularity of a lesion, Klüver-Barrera stain for degree of demyelination, Bodian stain for axonal density, and immunostaining of glial fibrillary acid protein for reactive astrocytes and fibrillary gliosis. Nineteen lesions were selected for analysis. Nearly all lesions were compatible with the chronic MS plaque: hypocellularity, absence of myelinated axons, in the presence of reactive astrocytes. Contrast ratios of the lesions were highly correlated (R = -0.90; p < 0.01), with degree of hypointensity scored semiquantitatively. Degree of hypointensity on T1-weighted SE images did not correlate with degree of demyelination or number of reactive astrocytes, but was associated with axonal density (R = -0.71; p = 0.001). A trend was found with degree of matrix destruction (R = 0.45; p = 0.052). We conclude that, in our limited sample, hypointense lesions seen on T1-weighted SE MR images are associated histopathologically with severe tissue destruction, including axonal loss. Our results need to be substantiated in a larger study on more varied patient material to evaluate the use of hypointense lesions as a surrogate marker of persistent deficit in MS patients.

MRI findings are increasingly used as outcome measures in therapeutic trials in MS. The discrepancy between the extent of the lesions on conventional T2 images and the clinical condition of the patient is one of the problems encountered in such studies. This clinical-radiological paradox prevents the use of MRI data as surrogate markers of disability in MS. A recent pilot study suggested a relationship between hypointense lesions on T1 MRI and disability. To assess in more detail the correlation of changes in hypointense lesion load on T1-weighted spin-echo MR images ("black holes") with changes in disability in MS, we studied 46 patients with clinically definite MS at baseline and after a median follow-up of 40 months. There was a significant correlation between baseline disability and hypointense lesion load (Spearman rank correlation coefficient [SRCC] = 0.46, p = 0.001). In secondary progressive patients, the rate of accumulation of these "black holes" was significantly related to progression rate (SRCC = 0.81, p < 0.0001). We speculate that the appearance of hypointense lesions is the MRI equivalent of a failure of remission. Overall, T1 lesion load measurements correlated better with clinical assessments than T2 lesion load measurements. Quantification of hypointense lesion load on T1-weighted spin-echo MRI helps to resolve the clinical-radiological paradox between disability and MRI and has the potential to be a surrogate marker of disability in MS.

Magnetic resonance imaging (MRI) monitoring of disease progression in multiple sclerosis is limited by the lack of correlation of abnormalities seen on T2‐weighted imaging, and disability. We studied the histopathology of multiple sclerosis lesions, as depicted by MRI, in a large postmortem sample, focusing on axonal loss. Tissue samples from 17 patients were selected immediately postmortem for histopathological analysis on the basis of T2‐weighted imaging, including normal appearing white matter and T1 hypointense lesions. In each region, we measured magnetization transfer ratios (MTR), T1 contrast ratio, myelin, and axonal density. T2 lesions (109 samples) were heterogeneous with regard to MRI appearance on T1 and MTR, whereas axonal density ranged from 0% (no residual axons) to 100% (normal axonal density). Of 64 T2 lesions, 17 were reactive (mild perivascular inflammation only), 21 active, 15 chronically active, and 11 chronically inactive. MTR and T1 contrast ratio correlated strongly with axonal density. Also in normal appearing white matter (24 samples), MTR correlated with axonal density. In conclusion, postmortem tissue sampling by using MRI revealed a range of pathology, illustrating the high sensitivity and low specificity of T2‐weighted imaging. T1 hypointensity and MTR were strongly associated with axonal density, emphasizing their role in monitoring progression in multiple sclerosis.

The authors compare the spinal cord magnetization transfer ratio (MTR) of multiple sclerosis (MS) patients to healthy volunteers, relate MTR to spinal cord atrophy, and relate these and other magnetic resonance (MR) imaging parameters to disability. Sixty-five patients with MS (14 relapsing remitting [RRL 34 secondary progressive [SPL and 17 primary progressive [PP] MS), and 9 healthy volunteers were studied using MR at 1 .0 T. Disability of the patients was assessed using the expanded disability status scale (EDSS). Magnetic resonance parameters were upper spinal cord MTR, number of focal spinal lesions, presence of diffuse abnormalities, and spinal cord cross-sectional area (CSA).Correlations were assessed using Spearman's rank correlation coefficient (r). Magnetization transfer ratio was higher in the controls (median, 33%; range, 30%-38%) than in patients with MS (median, 30%; range, 16-36; p < 0.05). In patients with MS, EDSS correlated with spinal cord MTR, albeit weakly (r = -0.25, p < 0.05). Correlation between EDSS and spinal cord CSA was better (SRCC = -0.40, p < 0.01 ). No correlation was found between MTR and CSA (r = 0.1, p = 0.4). Combining MTR with spinal cord CSA improved correlation with EDSS (r = -0.46, p < 0.001 ), suggesting an independent correlation between disability and these 2 MR parameters. Expanded dis-ability status scale scores were higher in patients who had diffuse spinal cord abnormality regardless of focal lesions (median, 6; range, 1.5-7.5) than in patients without diffuse abnormalities (median, 3.5; range, 0-8; p < 0.01). CSA was lower in patients with diffuse spinal cord abnormality (median, 62; range, 46-89 mm 2 ) than in patients without diffuse abnormalities (median, 73; range, 47-89 mm 2 ; p < 0.01). MTR was slightly lower in patients with diffuse spinal cord abnormalities (median, 29; range, 21 %-33%) than in patients without diffuse abnormalities (median, 31; range, 16-36; t-test, p < 0.05).

Objective: The long-term results and prognostic factors of radiofrequency ablation (RFA) for unresectable colorectal liver metastases (CRLM) in a single centre with .10 years of experience were retrospectively analysed. Methods: A total of 100 patients with unresectable colorectal liver metastases (CRLM) (size 0.2-8.3 cm; mean 2.4 cm) underwent a total of 126 RFA sessions (237 lesions). The mean follow-up time was 29 months (range 6-93 months). Lesion characteristics (size, number and location), procedure characteristics (percutaneous or intra-operative approach) and major and minor complications were carefully noted. Local control, mean survival time and recurrence-free and overall survival were statistically analysed. Results: No direct procedure-related deaths were observed. Major complications were present in eight patients. Local RFA site recurrence was 12.7% (n530/237); for tumour diameters of ,3 cm, 3-5 cm and .5 cm, recurrence was 5.6% (n58/143), 19.5% (n515/ 77) and 41.2% (n57/17), respectively. Centrally located lesions recurred more often than peripheral ones, at 21.4% (n521/98) vs 6.5% (n59/139), respectively, p50.009. Including additional treatments for recurring lesions when feasible, lesion-based local control reached 93%. The mean survival time from RFA was 56 (95% confidence interval (CI) 45-67) months. Overall 1-, 3-, 5-and 8-year survival from RFA was 93%, 77%, 36% and 24%, respectively. Conclusions: RFA for unresectable CRLM is a safe, effective and potentially curative treatment option; the long-term results are comparable with those of previous investigations employing surgical resection. Factors determining success are lesion size, the number of lesions and location. Colorectal carcinoma is one of the most common malignancies in Western countries. In 20-25% of patients with colorectal carcinoma (synchronous) liver metastases are present at the time of diagnosis of the primary tumour [1][2][3]. Another 20-30% of patients develop (metachronous) liver metastases, which usually arise within 3 years of initial treatment of the primary tumour [1,3]. In Europe and the USA, colorectal liver metastases (CRLM) are the most frequent cause of malignant hepatic tumours [4]. The prognosis of patients with untreated CRLM (receiving only symptomatic therapy) is poor, with a median survival rate of 4.5-12 months, depending on the extent of metastatic disease at the time of diagnosis [5]. Chemotherapeutics, using oxaliplatin and fluorouracil (5FU), can prolong survival in a palliative setting with a median survival of approximately 18 months [6][7][8]. More recent results show a median survival of 21.7 months for patients treated with capecitabine, irinotecan and oxaliplatin [9]. Surgical resection is still considered the only method for definite treatment of malignant liver tumours by many [10][11][12][13][14][15][16][17]. Resection of liver metastases with curative intent results in a 5 year overall survival rate of 24-58% and a 10 year survival rate of 28% [11][12][13][14][15][16][17][18][19]. It is not ...