Lumbar disc extrusions reduce faster than bulging discs due to an active role of macrophages in sciatica.

OBJECTIVE: This retrospective observational histological study aims to associate the size and type of disc herniation with the degree of macrophage infiltration in disc material retrieved during disc surgery in patients with sciatica. METHODS: Disc tissue of 119 sciatica patients was embedded in paraffin and stained with hematoxylin and CD68. Tissue samples were categorized as mild (0-10/cm2), moderate (10-100/cm2), and considerable (> 100/cm2) macrophage infiltration. All 119 patients received an MRI at baseline, and 108 received a follow-up MRI at 1-year. MRIs were reviewed for the size and type of the disc herniations, and for Modic changes in the vertebral endplates. RESULTS: Baseline characteristics and duration of symptoms before surgery were comparable in all macrophage infiltration groups. The degree of macrophage infiltration was not associated with herniation size at baseline, but significantly associated with reduction of size of the herniated disc at 1-year post surgery. Moreover, the degree of macrophage infiltration was higher in extrusion in comparison with bulging (protrusion) of the disc. Results were comparable in patients with and without Modic changes. CONCLUSION: Macrophage infiltration was positively associated with an extruded type of disc herniation as well as the extent of reduction of the herniated disc during 1-year follow-up in patients with sciatica. This is an indication that the macrophages play an active role in reducing herniated discs. An extruded disc herniation has a larger surface for the macrophages to adhere to, which leads to more size reduction.

Data-efficient deep learning of radiological image data for outcome prediction after endovascular treatment of patients with acute ischemic stroke.

Treatment selection is becoming increasingly more important in acute ischemic stroke patient care. Clinical variables and radiological image biomarkers (old age, pre-stroke mRS, NIHSS, occlusion location, ASPECTS, among others) have an important role in treatment selection and prognosis. Radiological biomarkers require expert annotation and are subject to inter-observer variability. Recently, Deep Learning has been introduced to reproduce these radiological image biomarkers. Instead of reproducing these biomarkers, in this work, we investigated Deep Learning techniques for building models to directly predict good reperfusion after endovascular treatment (EVT) and good functional outcome using CT angiography images. These models do not require image annotation and are fast to compute. We compare the Deep Learning models to Machine Learning models using traditional radiological image biomarkers. We explored Residual Neural Network (ResNet) architectures, adapted them with Structured Receptive Fields (RFNN) and auto-encoders (AE) for network weight initialization. We further included model visualization techniques to provide insight into the network's decision-making process. We applied the methods on the MR CLEAN Registry dataset with 1301 patients. The Deep Learning models outperformed the models using traditional radiological image biomarkers in three out of four cross-validation folds for functional outcome (average AUC of 0.71) and for all folds for reperfusion (average AUC of 0.65). Model visualization showed that the arteries were relevant features for functional outcome prediction. The best results were obtained for the ResNet models with RFNN. Auto-encoder initialization often improved the results. We concluded that, in our dataset, automated image analysis with Deep Learning methods outperforms radiological image biomarkers for stroke outcome prediction and has the potential to improve treatment selection.

Clinical applicability of and changes in perfusion MR imaging in brain metastases after stereotactic radiotherapy.

To assess the applicability of perfusion-weighted (PWI) magnetic resonance (MR) imaging in clinical practice, as well as to evaluate the changes in PWI in brain metastases before and after stereotactic radiotherapy (SRT), and to correlate these changes to tumor status on conventional MR imaging. Serial MR images at baseline and at least 3 and 6 months after SRT were retrospectively evaluated. Size of metastases and the relative cerebral blood volume (rCBV), assessed with subjective visual inspection in the contrast enhanced area, were evaluated at each time point. Tumor behavior of metastases was categorized into four groups based on predefined changes on MRI during follow-up, or on histologically confirmed diagnosis; progressive disease (PD), pseudoprogression (PsPD), non-progressive disease (non-PD) and progression unspecified (PU). Twenty-six patients with 42 metastases were included. Fifteen percent (26/168) of all PW images could not be evaluated due to localization near large vessels or the scalp, presence of hemorrhage artefacts, and in 31% (52/168) due to unmeasurable residual metastases. The most common pattern (52%, 13/25 metastases) showed a high rCBV at baseline and low rCBV during follow-up, occurring in metastases with non-PD (23%, 3/13), PsPD (38%, 5/13) and PU (38%, 5/13). Including only metastases with a definite outcome generally showed low rCBV in PsPD or non-PD, and high rCBV in PD. Although non-PD and PsPD may be distinguished from PD after SRT using the PW images, the large proportion of images that could not be assessed due to artefacts and size severely hampers value of PWI in predicting tumor response after SRT.

Comparison of CTA- and DSA-Based Collateral Flow Assessment in Patients with Anterior Circulation Stroke.

BACKGROUND AND PURPOSE: Collateral flow is associated with clinical outcome after acute ischemic stroke and may serve as a parameter for patient selection for intra-arterial therapy. In clinical trials, DSA and CTA are 2 imaging modalities commonly used to assess collateral flow. We aimed to determine the agreement between collateral flow assessment on CTA and DSA and their respective associations with clinical outcome. MATERIALS AND METHODS: Patients randomized in MR CLEAN with middle cerebral artery occlusion and both baseline CTA images and complete DSA runs were included. Collateral flow on CTA and DSA was graded 0 (absent) to 3 (good). Quadratic weighted κ statistics determined agreement between both methods. The association of both modalities with mRS at 90 days was assessed. Also, association between the dichotomized collateral score and mRS 0-2 (functional independence) was ascertained. RESULTS: Of 45 patients with evaluable imaging data, collateral flow was graded on CTA as 0, 1, 2, 3 for 3, 10, 20, and 12 patients, respectively, and on DSA for 12, 17, 10, and 6 patients, respectively. The κ-value was 0.24 (95% CI, 0.16-0.32). The overall proportion of agreement was 24% (95% CI, 0.12-0.38). The adjusted odds ratio for favorable outcome on mRS was 2.27 and 1.29 for CTA and DSA, respectively. The relationship between the dichotomized collateral score and mRS 0-2 was significant for CTA (P = .01), but not for DSA (P = .77). CONCLUSIONS: Commonly applied collateral flow assessment on CTA and DSA showed large differences, indicating that these techniques are not interchangeable. CTA was significantly associated with mRS at 90 days, whereas DSA was not.

Interobserver variability in the radiological assessment of magnetic resonance imaging (MRI) including perfusion MRI in glioblastoma multiforme.

BACKGROUND AND PURPOSE: Conventional magnetic resonance imaging (MRI) has limited value for differentiation of true tumor progression and pseudoprogression in treated glioblastoma multiforme (GBM). Perfusion weighted imaging (PWI) may be helpful in the differentiation of these two phenomena. Here interobserver variability in routine radiological evaluation of GBM patients is assessed using MRI, including PWI. METHODS: Three experienced neuroradiologists evaluated MR scans of 28 GBM patients during temozolomide chemoradiotherapy at three time points: preoperative (MR1) and postoperative (MR2) MR scan and the follow-up MR scan after three cycles of adjuvant temozolomide (MR3). Tumor size was measured both on T1 post-contrast and T2 weighted images according to the Response Assessment in Neuro-Oncology criteria. PW images of MR3 were evaluated by visual inspection of relative cerebral blood volume (rCBV) color maps and by quantitative rCBV measurements of enhancing areas with highest rCBV. Image interpretability of PW images was also scored. Finally, the neuroradiologists gave a conclusion on tumor status, based on the interpretation of both T1 and T2 weighted images (MR1, MR2 and MR3) in combination with PWI (MR3). RESULTS: Interobserver agreement on visual interpretation of rCBV maps was good (κ = 0.63) but poor on quantitative rCBV measurements and on interpretability of perfusion images (intraclass correlation coefficient 0.37 and κ = 0.23, respectively). Interobserver agreement on the overall conclusion of tumor status was moderate (κ = 0.48). CONCLUSIONS: Interobserver agreement on the visual interpretation of PWI color maps was good. However, overall interpretation of MR scans (using both conventional and PW images) showed considerable interobserver variability. Therefore, caution should be applied when interpreting MRI results during chemoradiation therapy.

Safety of intra-arterial treatment in acute ischaemic stroke patients on oral anticoagulants. A cohort study and systematic review.

BACKGROUND AND PURPOSE: An elevated international normalized ratio (INR) of >1.7 is a contraindication for the use of intravenous thrombolytics in acute ischaemic stroke. Local intra-arterial therapy (IAT) is considered a safe alternative. The safety and outcome of IAT were investigated in patients with acute ischaemic stroke using oral anticoagulants (OACs). METHODS: Data were obtained from a large national Dutch database on IAT in acute stroke patients. Patients were categorized according to the INR: >1.7 and ≤1.7. Primary outcome was symptomatic intracerebral hemorrhage (sICH), defined as deterioration in the National Institutes of Health Stroke Scale score of ≥4 and ICH on brain imaging. Secondary outcomes were clinical outcome at discharge and 3 months. Occurrence of outcomes was compared with risk ratios and corresponding 95% confidence intervals. Further, a systematic review and meta-analysis on sICH risk in acute stroke patients on OACs treated with IAT was performed. RESULTS: Four hundred and fifty-six patients were included. Eighteen patients had an INR > 1.7 with a median INR of 2.4 (range 1.8-4.1). One patient (6%) in the INR > 1.7 group developed a sICH compared with 53 patients (12%) in the INR ≤ 1.7 group (risk ratio 0.49, 95% confidence interval 0.07-3.13). Clinical outcomes did not differ between the two groups. Our meta-analysis showed a first week sICH risk of 8.1% (95% confidence interval 3.9%-17.1%) in stroke patients with elevated INR treated with IAT. CONCLUSION: The use of OACs, leading to an INR > 1.7, did not seem to increase the risk of an sICH in patients with an acute stroke treated with IAT.

Thrombectomy in posterior circulation stroke through persistent primitive trigeminal artery: A case report.

We describe a case of intra-arterial treatment (IAT) of acute posterior circulation occlusion in a patient with a persistent primitive trigeminal artery (PPTA). The patient presented with an acute left sided hemiparesis and loss of consciousness (Glasgow coma score of 5). Computed tomography angiography showed an acute occlusion of the right internal carotid artery (ICA), the PPTA, distal basilar artery (BA), right posterior cerebral artery (PCA), and right superior cerebellar artery (SCA). Stent-retriever assisted thrombectomy was not considered possible through the hypoplastic proximal BA. After passage of the proximal ICA occlusion, the right PCA and SCA were recanalized through the PPTA, with a single thrombectomy procedure. Ten days after intervention patient was discharged scoring optimal EMV with only a mild facial and left hand paresis remaining. PPTA is a persistent embryological carotid-basilar connection. Knowledge of existing (embryonic) variants in neurovascular anatomy is essential when planning and performing acute neurointerventional procedures.

Interobserver agreement on MRI evaluation of patients with cervical radiculopathy.

AIM: To evaluate the interobserver agreement on magnetic resonance imaging (MRI) evaluation of herniated discs, spondylotic neuroforaminal stenosis, and root compression in patients with recent onset cervical radiculopathy and in addition, to assess the added value of disclosure of clinical information to interobserver agreement. MATERIALS AND METHODS: The MRI images of 82 patients with less than 1 month of symptoms and signs of cervical radiculopathy were evaluated independently by two neuroradiologists who were unaware of clinical findings. MRI analysis was repeated after disclosure of clinical information. Interobserver agreement was calculated using kappa statistics. RESULTS: The kappa score for evaluation of herniated discs and of spondylotic foramen stenosis was 0.59 and 0.63, respectively. A kappa score of 0.67 was found for the presence of root compression. After disclosure of clinical information kappa scores increased slightly: from 0.59 to 0.62 for the detection of herniated discs, from 0.63 to 0.66 for spondylotic foramen stenosis, and from 0.67 to 0.76 for root compression. CONCLUSION: Interobserver reliability of MRI evaluation in patients with cervical radiculopathy was substantial for root compression, with or without clinical information. Agreement on the cause of the compression, i.e., herniated disc or spondylotic foraminal stenosis, was lower.

Radiosurgery of brain arteriovenous malformations in children.

OBJECTIVE: The authors describe their experience in treating 22 children with a single brain arteriovenous malformation (bAVM) using a dedicated LINAC stereotactic radiosurgery unit. METHODS: The findings of 22 consecutive patients < or = 18 years of age who underwent radiosurgery for a single bAVM and with at least 24 months of follow-up, or earlier proven obliteration,were reviewed. The median age at radiosurgery was 13.8 years,with a hemorrhagic presentation in 86%. Median bAVM-volume was 1.8 ml, with a median prescribed marginal dose of 19.0 Gy. RESULTS: The crude complete obliteration-rate was 68% (n = 15) after a median follow-up of 24 months. The actuarial obliteration- rate was 45 % after two years and 64 % after three years. Patients with a radiosurgery-based AVM score < or = 1 more frequently had an excellent outcome than patients with a bAVM score > 1 (71% vs. 20%, P = 0.12), as well as an increased obliteration rate (P = 0.03) One patient died from a bAVM-related hemorrhage 27 months after radiosurgery, representing a postradiosurgery hemorrhage rate of 1.3%/year for the complete followup interval. Overall outcome was good to excellent in 68% (n = 15). Radiation-induced changes on MR imaging were seen in 36% (n = 8) after a median interval of 12.5 months, resulting in deterioration of pre-existing neurological symptoms in one patient. CONCLUSIONS: Radiosurgery is a relatively effective, minimally invasive treatment for small bAVMs in children. The rebleeding rate is low, provided that known predilection places for bleeding had been endovascularly eliminated.Our overall results compare unfavourably to recent pediatric microsurgical series, although comparison between series remains imprecise. Nevertheless, when treatment is indicated in a child with a bAVM that is amenable to both microsurgery or radiosurgery, microsurgery should carefully be advocated over radiosurgery, because of its immediate risk reduction.

Reduction of brain volume in MS. MRI and pathology findings.

Atrophy is one of the hallmarks in multiple sclerosis (MS), especially in the advanced stage. Modern magnetic resonance (MR) techniques can reliably measure brain volume and changes therein. Depending on the technique used, changes of about 1% may be detected. Clinicoradiological studies show good correlation between atrophy measures, both in brain and spinal cord, and clinical measures. The exact relationship between focal MS lesions and global atrophy has yet to be established. Number of lesions early in the disease seems to predict later atrophy. The exact pathomechanism of atrophy in MS probably may be explained by both demyelination and axonal loss--which may occur independently from each other.

Spinal cord abnormalities in recently diagnosed MS patients: added value of spinal MRI examination.

OBJECTIVE: The most recent diagnostic criteria for multiple sclerosis (MS) ascertain that findings from spinal cord MRI can be used to demonstrate dissemination in space. Because little is known about the prevalence and characteristics of cord lesions early in the disease, the authors studied the prevalence of spinal cord abnormalities in patients with early-stage MS and assessed their impact on diagnostic classification. METHODS: The brains and spinal cords of 104 recently diagnosed patients with MS were examined. Median interval between first symptom and diagnosis was 18.4 months. The brain MRI protocol included before and after gadolinium axial T1-weighted conventional spin-echo sequences and dual-echo spin-echo images. For spinal cord MRI, sagittal cardiac-triggered dual-echo T2-weighted and sagittal T1-weighted spin-echo images were included. Clinical assessment for each patient included age, sex, clinical signs for spinal cord involvement, and Expanded Disability Status Scale. RESULTS: Abnormal cord MRIs were found in 83% of patients, usually with only focal lesions. Diffuse cord abnormalities were found in 13% of patients, although in isolation they were found in only three patients. Focal cord lesions were often multiple (median number, 3.0), small (median, 0.8 vertebral segments), and primarily (56.4%) situated in the cervical spinal cord. In 68 of 104 patients (65.4%), two or more focal lesions were visible on spinal cord images. The criteria for dissemination in space, as defined in the McDonald criteria for the brain, were met in only 66.3% of the patients. This percentage increased to 84.6% when spinal cord MRI abnormalities were also included. CONCLUSION: Spinal cord abnormalities are prevalent in patients with early-stage MS, have distinct morphologic characteristics, and help to determine dissemination in space at time of diagnosis.

Axonal damage in the spinal cord of MS patients occurs largely independent of T2 MRI lesions.

OBJECTIVE: To determine the degree of axonal damage in relationship to signal abnormalities on T2-weighted high-resolution MRI in spinal cord tissue of patients with MS. METHODS: Spinal cord specimens of nine patients with MS and four controls were imaged at high resolution (4.7 T) in an axial plane and scored for lesions with increased signal intensity (SI). Histopathologic sections were cut and immunostained with NE14 (neurofilament marker) and Luxol fast blue (myelin stain). For each area, axonal density and diameter were quantified; axonal irregularity, NE14 axonal staining intensity, and myelin content were semiquantitatively scored. Included were 209 areas from MS cases and 109 areas from control cases distributed over lateral, posterior, and anterior columns. RESULTS: In control cases, no SI changes were found, average density of axons was 26,989/mm(2), average diameter was 1.1 micro m, and all scores for axonal irregularity, NE14 staining intensity, and myelin were normal. In MS cases, areas with increased SI were found, average axonal density was 11,807/mm(2) (p < 0.0001), and average axonal diameter 2.0 micro m (p = 0.001). Areas with high SI on MRI had lowest axonal density (average count: 10,504/mm(2); range: 3,433 to 26,325/mm(2)), largest diameter (average: 2.3 micro m; range: 1.0 to 4.0 micro m), and highest axonal irregularity and NE14 staining intensity compared to normal appearing cord tissue (NACT). However, NACT of MS cases also had lower axonal density (14,158/mm(2)) and higher average axonal diameter (1.6 micro m) than controls. CONCLUSIONS: Marked axonal loss occurs in MS spinal cords, largely independent of the degree of signal abnormality on T2-weighted MRI.

Hypointense lesions on T1-weighted spin-echo magnetic resonance imaging: relation to clinical characteristics in subgroups of patients with multiple sclerosis.

CONTEXT: Hypointense lesions on T1-weighted spin-echo magnetic resonance images (T1 lesions) represent destructive multiple sclerosis (MS) lesions, consisting of axonal loss and matrix destruction. These lesions are being used as a secondary outcome measure in phase III clinical trials. Clinical determinants of T1 lesions may differ between subgroups of patients with MS and subsequently may have implications for the selection of patients for clinical trials. OBJECTIVE: To determine if clinical characteristics of patients with MS are related to T1 lesion volume. DESIGN: A survey of 138 patients with MS (52 with relapsing-remitting MS, 44 with secondary progressive MS, and 42 with primary progressive MS). SETTING: The Magnetic Resonance Center for Multiple Sclerosis Research, University Hospital "Vrije Universiteit," Amsterdam, the Netherlands. MAIN OUTCOME MEASURES: Type of MS, Expanded Disability Status Scale (EDSS) score, sex, age at first symptoms, and T1 lesion volume. RESULTS: Patients with secondary progressive MS have the highest T1 lesion volume. Patients with relapsing-remitting MS have a lower T1/T2 ratio than patients with secondary progressive MS and patients with primary progressive MS. In patients with relapsing-remitting MS and secondary progressive MS, T1 lesion volume relates to disease duration and EDSS score, while in patients with primary progressive MS sex is important. A trend toward higher T1 lesion volume was shown for male patients with primary progressive MS when compared with female patients with primary progressive MS (1.0 cm(3) vs 0.3 cm(3), P=.03); a trend toward higher T1 lesion volume was found with age at onset in patients with relapsing-remitting MS and in patients with primary progressive MS. CONCLUSIONS: In patients with MS different clinical characteristics associate with T1 lesion volume, suggesting a more destructive type of lesions in certain subgroups. A possible sex difference in (destructive) lesion development on magnetic resonance imaging should be evaluated in more detail, preferably in a cohort.

Comparison of a conventional cardiac-triggered dual spin-echo and a fast STIR sequence in detection of spinal cord lesions in multiple sclerosis.

The current optimal imaging protocol in spinal cord MR imaging in patients with multiple sclerosis includes a long TR conventional spin-echo (CSE) sequence, requiring long acquisition times. Using short tau inversion recovery fast spin-echo (fast STIR) sequences both acquisition time can be shortened and sensitivity in the detection of multiple sclerosis (MS) abnormalities can be increased. This study compares both sequences for the potential to detect both focal and diffuse spinal abnormalities. Spinal cords of 5 volunteers and 20 MS patients were studied at 1.0 T. Magnetic resonance imaging included cardiac-gated sagittal dual-echo CSE and a cardiac-gated fast STIR sequence. Images were scored regarding number, size, and location of focal lesions, diffuse abnormalities and presence/hindrance of artifacts by two experienced radiologists. Examinations were scored as being definitely normal, indeterminate, or definitely abnormal. Interobserver agreement regarding focal lesions was higher for CSE (kappa = 0.67) than for fast STIR (kappa = 0.57) but did not differ significantly. Of all focal lesions scored in consensus, 47% were scored on both sequences, 31% were only detected by fast STIR, and 22% only by dual-echo CSE (n.s.). Interobserver agreement for diffuse abnormalities was lower with fast STIR (kappa = 0.48) than dual-echo CSE (kappa = 0.65; n. s.). After consensus, fast STIR showed in 10 patients diffuse abnormalities and dual-echo CSE in 3. After consensus, in 19 of 20 patients dual-echo CSE scans were considered as definitely abnormal compared with 17 for fast STIR. The fast STIR sequence is a useful adjunct to dual-echo CSE in detecting focal abnormalities and is helpful in detecting diffuse MS abnormalities in the spinal cord. Due to the frequent occurrence of artifacts and the lower observer concordance, fast STIR cannot be used alone.

Magnetization transfer ratio of the spinal cord in multiple sclerosis: relationship to atrophy and neurologic disability.

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 [RR], 34 secondary progressive [SP], 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 disability 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 mm2) than in patients without diffuse abnormalities (median, 73; range, 47-89 mm2; 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).

Linomide in the treatment of multiple sclerosis: MRI results from prematurely terminated phase-III trials.

Due to an unexpected increase in serious cardiovascular events in MS patients treated with Linomide, a synthetic immunomodulator, two phase-III multinational relapsing remitting (RR) and secondary progressive (SP) MS trials had to be discontinued. MRI results of 413 patients who participated for at least 3 months were analysed. Patients received placebo, 2.5 or 5 mg Linomide. Scans were performed at pre-enrolment, month 3 and termination. The number and volume of enhancing lesions (ELV), and the number of active scans were evaluated. At month 3, the decrease in the number of enhancing lesions in the placebo group was 11%, compared with 15% in the 2.5 mg group (P=0.027) and 23% in the 5 mg group (P=0.057). Using the percentage of active scans as outcome parameter, the odds ratio for improvement between placebo and 2.5 mg group was 1.62 (P=0.14); between placebo and 5 mg Linomide group 3.58 (P=0.003). At termination, a rebound effect was noted in the 2.5 mg group (P=0.01). Analysis of the ELV showed no significant difference between placebo and treatment groups. Although Linomide has unacceptable side effects, it seems to have a modest effect on MS disease activity, as measured by MRI. Multiple Sclerosis (2000) 6, 99 - 104

Spinal cord magnetic resonance imaging in suspected multiple sclerosis.

We examined the value of spinal cord magnetic resonance imaging (MRI) in the diagnostic work-up of multiple sclerosis (MS). Forty patients suspected of having MS were examined within 24 months after the start of symptoms. Disability was assessed, and symptoms were categorized as either brain or spinal cord. Work-up further included cerebrospinal fluid analysis and standard proton-density, T2-, and T1-weighted gadolinium-enhanced brain and spinal cord MRI. Patients were categorized as either clinically definite MS (n = 13), laboratory-supported definite MS (n = 14), or clinically probable MS (n = 4); four patients had clinically probable MS, and in nine MS was suspected. Spinal cord abnormalities were found in 35 of 40 patients (87.5 %), consisting of focal lesions in 31, only diffuse abnormalities in two, and both in two. Asymptomatic spinal cord lesions occurred in six patients. All patients with diffuse spinal cord abnormality had clear spinal cord symptoms and a primary progressive disease course. In clinically definite MS, the inclusion of spinal imaging increased the sensitivity of MRI to 100 %. Seven patients without a definite diagnosis had clinically isolated syndromes involving the spinal cord. Brain MRI was inconclusive, while all had focal spinal cord lesions which explained symptoms and ruled out other causes. Two other patients had atypical brain abnormalities suggesting ischemic/vascular disease. No spinal cord abnormalities were found, and during follow-up MS was ruled out. Spinal cord abnormalities are common in suspected MS, and may occur asymptomatic. Although diagnostic classification is seldom changed, spinal cord imaging increases diagnostic sensitivity of MRI in patients with suspected MS. In addition, patients with primary progressive MS may possibly be earlier diagnosed. Finally, differentiation with atypical lesions may be improved.

Functional MRI: background and clinical applications.

Functional MRI is gaining wider acceptance as a clinical tool that can be used for a variety of clinical indications. The goal of this article is to introduce the reader to functional MRI as a technique and present some clinical applications of functional MRI.

Axonal loss in multiple sclerosis lesions: magnetic resonance imaging insights into substrates of disability.

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.

Development of hypointense lesions on T1-weighted spin-echo magnetic resonance images in multiple sclerosis: relation to inflammatory activity.

OBJECTIVE: To evaluate whether degree of inflammatory activity in multiple sclerosis, expressed by frequency of gadolinium enhancement, has prognostic value for development of hypointense lesions on T1-weighted spin-echo magnetic resonance images, a putative marker of tissue destruction. DESIGN: Cohort design with long-term follow-up. Thirty-eight patients with multiple sclerosis who in the past had been monitored with monthly gadolinium-enhanced magnetic resonance imaging for a median period of 10 months (range, 6-12 months) were reexamined after a median period of 40.5 months (range, 33-80 months). SETTING: Magnetic Resonance Center for Multiple Sclerosis Research, Amsterdam, the Netherlands, referral center. MAIN OUTCOME MEASURES: The new enhancing lesion rate (median number of gadolinium-enhancing lesions per monthly scan) during initial monthly follow-up; hypointense T1 and hyperintense T2 lesion load at first and last visit. RESULTS: The number of enhancing lesions on entry scan correlated with the new enhancing lesions rate (r = 0.64; P<.001, Spearman rank correlation coefficient). The new enhancing lesion rate correlated with yearly increase in T1 (r = 0.42; P<.01, Spearman rank correlation coefficient) and T2 (r = 0.47; P<.01, Spearman rank correlation coefficient) lesion load. Initial T1 lesion load correlated more strongly with yearly increase in T1 lesion load (r = 0.68; P<.01, Spearman rank correlation coefficient). CONCLUSIONS: Degree of inflammatory activity only partially predicted increase in T1 (and T2) lesion load at long-term follow-up. Initial T1 lesion load strongly contributed to subsequent increase in hypointense T1 lesion load, suggesting that there is a subpopulation of patients with multiple sclerosis who are prone to develop destructive lesions.