Second surgery for progressive glioblastoma: a multi-centre questionnaire and cohort-based review of clinical decision-making and patient outcomes in current practice.

PURPOSE: Glioblastoma prognosis is poor. Treatment options are limited at progression. Surgery may benefit, but no quality guidelines exist to inform patient selection. We sought to describe variations in surgical management at progression, highlight where further evidence is needed, and build towards a consensus strategy. METHODS: Current practice in selection of patients with progressive GBM for second surgery was surveyed online amongst specialists in the UK and Europe. We complemented this with an assessment of practice in a retrospective cohort study from six United Kingdom neurosurgical units. We used descriptive statistics to analyse the data. RESULTS: 234 questionnaire responses were received. Maintaining or improving patient quality of life was key to decision making, with variation as to whether patient age, performance status or intended extent of resection was relevant. MGMT methylation status was not important. Half considered no minimum time after first surgery. 288 patients were reported in the cohort analysis. Median time to second surgery from first surgery 390 days. Median overall survival 815 days, with no association between time to second surgery and time to death (p = 0.874). CONCLUSIONS: This is the most wide-ranging examination of contemporaneous practice in management of GBM progression. Without evidence-based guidelines, the variation is unsurprising. We propose consensus guidelines for consideration, to reduce heterogeneity in decision making, support data collection and analysis of factors influencing outcomes, and to inform clinical trials to establish whether second surgery improves patient outcomes, or simply selects to patients already performing well.

White matter changes in the perforant path area in patients with amyotrophic lateral sclerosis.

OBJECTIVE: The aim of this study was to test the hypothesis that white matter degeneration of the perforant path - as part of the Papez circuit - is a key feature of amyotrophic lateral sclerosis (ALS), even in the absence of frontotemporal dementia (FTD) or deposition of pTDP-43 inclusions in hippocampal granule cells. METHODS: We used diffusion Magnetic Resonance Imaging (dMRI), polarized light imaging (PLI) and immunohistochemical analysis of post mortem hippocampus specimens from controls (n = 5) and ALS patients (n = 14) to study white matter degeneration in the perforant path. RESULTS: diffusion Magnetic Resonance Imaging demonstrated a decrease in fractional anisotropy (P = 0.01) and an increase in mean diffusivity (P = 0.01) in the perforant path in ALS compared to controls. PLI-myelin density was lower in ALS (P = 0.05) and correlated with fractional anisotropy (r = 0.52, P = 0.03). These results were confirmed by immunohistochemistry; both myelin (proteolipid protein, P = 0.03) and neurofilaments (SMI-312, P = 0.02) were lower in ALS. Two out of the fourteen ALS cases showed pTDP-43 pathology in the dentate gyrus, but with comparable myelination levels in the perforant path to other ALS cases. CONCLUSION: We conclude that degeneration of the perforant path occurs in ALS patients and that this may occur before, or independent of, pTDP-43 aggregation in the dentate gyrus of the hippocampus. Future research should focus on correlating the degree of cognitive decline to the amount of white matter atrophy in the perforant path.

Epilepsy and adverse quality of life in surgically resected meningioma.

OBJECTIVES: Meningiomas are common intracranial tumors, and despite surgery or therapy with anti-epileptic drugs (AEDs), many patients suffer from seizures. Epilepsy has a significant impact on quality of life (QoL) in non-tumor populations, but the impact of epilepsy on QoL in patients with meningioma is unknown. Our aim was to evaluate the impact of epilepsy on QoL in patients that have undergone resection of a benign meningioma. MATERIALS AND METHODS: We recruited meningioma patients without epilepsy (n=109), meningioma patients with epilepsy (n=56), and epilepsy patients without meningioma (n=64). QoL was measured with the Short Form 36 version 2 (SF-36), the Functional Assessment of Cancer Therapy (FACT-BR), and the Liverpool Adverse Events Profile (LAEP). Regression analyses identified significant determinants of QoL. RESULTS: Patients with meningioma and epilepsy had poorer QoL scores than meningioma patients without epilepsy in all measures. In FACT-BR, this difference was significant. Multiple regression analyses demonstrated that current AED use had a greater impact on QoL scores than recent seizures. Other variables associated with impaired QoL included depression, unemployment, and meningioma attributed symptoms. CONCLUSIONS: Epilepsy has a negative impact on quality of life in patients with benign meningioma. AED use is correlated with impaired QoL and raised LAEP scores, suggesting that AEDs and adverse effects may have led to impaired QoL in our meningioma patients with epilepsy. The severity of epilepsy in our meningioma population was comparatively mild; therefore, a more conservative approach to AED therapy may be indicated in an attempt to minimize adverse effects.

A Randomised Phase II Trial of Hippocampal Sparing Versus Conventional Whole Brain Radiotherapy After Surgical Resection or Radiosurgery in Favourable Prognosis Patients With 1-10 Brain Metastases.

AIMS: To assess in patients with 1-10 brain metastases, each of which has been treated by neurosurgery or stereotactic radiosurgery, whether hippocampal sparing whole brain radiotherapy (HS-WBRT) better spares neurocognitive function (NCF) than standard WBRT. Further, to assess whether a phase III randomised trial of HS-WBRT would be feasible in the UK. MATERIALS AND METHODS: A multicentre, randomised, open label phase II trial was undertaken, randomising patients to 30Gy in 10 fractions of WBRT or HS-WBRT. The primary endpoint was decline in Total recall using Hopkins Verbal Learning Test Revised (HVLT-R) at 4 months post treatment. To assess this, we aimed to recruit 84 patients over 3 years. Secondary endpoints included further measures of NCF, quality of life, duration of functional independence, local control of treated metastases, development of new metastases, disease control within the hippocampal regions, overall survival, steroid and antiepileptic medication requirements, and toxicity. RESULTS: The trial closed prematurely due to slower than anticipated recruitment. From April 2016 to January 2018, 23 patients were randomised. Follow up was a median of 25 months. Fifteen patients (6 WBRT, 9 HS-WBRT) were assessed for the primary endpoint; of these, 1 in each arm experienced significant decline in the 4-month HVLT-R Total recall score (p = 0.8). Patients in the HS-WBRT arm experienced less insomnia (p < 0.01) and drowsiness (p < 0.01). There were no differences in other secondary endpoints. CONCLUSION: A phase III randomised trial of HS-WBRT was shown not to be feasible at this time in the UK. As most randomised trials of HS-WBRT reported to date share common endpoints, including NCF, an individual patient data meta-analysis should be undertaken.

Is stereotactic radiosurgery under-utilised in the treatment of surgically excisable cerebral metastases?

BACKGROUND/OBJECTIVE: Brain metastases are a significant cause of morbidity and mortality. Treatment options included surgery, whole brain radiotherapy and stereotactic radiosurgery alone or in combination. There has been a significant increase in stereotactic radiosurgery (SRS) provision in the UK over the last 5 years. We investigated the proportion of surgically resected brain metastases that would be suitable for SRS. METHODS: We retrospectively collected data on 116 consecutive patients undergoing surgical resection of brain metastases. Suitable radiological targets for SRS were defined as solid tumours < 30 mm maximum diameter with no hydrocephalus and no symptomatic mass effect. RESULTS: One hundred and two cases (88%) were solitary metastasis and fourteen (12%) had multiple metastases. Median maximum tumour diameter was 34 mm (range: 12-70 mm). Approximately one-third of patients (n = 41) had surgically resected brain metastasis suitable for SRS. Median OS was 7.7 months for those suitable for SRS and 5.4 months for those not suitable for SRS (Fig. 3; Log Rank: P = 0.52). CONCLUSIONS: In surgically amenable tumours, day case SRS could also be used in approximately one-third of cases, thereby avoiding craniotomy and reducing length of stay. These data may be useful in planning service provision, and for drawing up business plans for a new SRS services. Nationally agreed guidelines for SRS for brain metastases have been developed and a full health economic analysis warrants further investigation to determine the cost effectiveness of SRS compared to craniotomy.

Optimizing parameter choice for FSL-Brain Extraction Tool (BET) on 3D T1 images in multiple sclerosis.

BACKGROUND: Brain atrophy studies often use FSL-BET (Brain Extraction Tool) as the first step of image processing. Default BET does not always give satisfactory results on 3DT1 MR images, which negatively impacts atrophy measurements. Finding the right alternative BET settings can be a difficult and time-consuming task, which can introduce unwanted variability. AIM: To systematically analyze the performance of BET in images of MS patients by varying its parameters and options combinations, and quantitatively comparing its results to a manual gold standard. METHODS: Images from 159 MS patients were selected from different MAGNIMS consortium centers, and 16 different 3DT1 acquisition protocols at 1.5 T or 3T. Before running BET, one of three pre-processing pipelines was applied: (1) no pre-processing, (2) removal of neck slices, or (3) additional N3 inhomogeneity correction. Then BET was applied, systematically varying the fractional intensity threshold (the "f" parameter) and with either one of the main BET options ("B" - bias field correction and neck cleanup, "R" - robust brain center estimation, or "S" - eye and optic nerve cleanup) or none. For comparison, intracranial cavity masks were manually created for all image volumes. FSL-FAST (FMRIB's Automated Segmentation Tool) tissue-type segmentation was run on all BET output images and on the image volumes masked with the manual intracranial cavity masks (thus creating the gold-standard tissue masks). The resulting brain tissue masks were quantitatively compared to the gold standard using Dice overlap coefficient (DOC). Normalized brain volumes (NBV) were calculated with SIENAX. NBV values obtained using for SIENAX other BET settings than default were compared to gold standard NBV with the paired t-test. RESULTS: The parameter/preprocessing/options combinations resulted in 20,988 BET runs. The median DOC for default BET (f=0.5, g=0) was 0.913 (range 0.321-0.977) across all 159 native scans. For all acquisition protocols, brain extraction was substantially improved for lower values of "f" than the default value. Using native images, optimum BET performance was observed for f=0.2 with option "B", giving median DOC=0.979 (range 0.867-0.994). Using neck removal before BET, optimum BET performance was observed for f=0.1 with option "B", giving median DOC 0.983 (range 0.844-0.996). Using the above BET-options for SIENAX instead of default, the NBV values obtained from images after neck removal with f=0.1 and option "B" did not differ statistically from NBV values obtained with gold-standard. CONCLUSION: Although default BET performs reasonably well on most 3DT1 images of MS patients, the performance can be improved substantially. The removal of the neck slices, either externally or within BET, has a marked positive effect on the brain extraction quality. BET option "B" with f=0.1 after removal of the neck slices seems to work best for all acquisition protocols.

A Comparison of Cranial Cavity Extraction Tools for Non-contrast Enhanced CT Scans in Acute Stroke Patients.

Cranial cavity extraction is often the first step in quantitative neuroimaging analyses. However, few automated, validated extraction tools have been developed for non-contrast enhanced CT scans (NECT). The purpose of this study was to compare and contrast freely available tools in an unseen dataset of real-world clinical NECT head scans in order to assess the performance and generalisability of these tools. This study included data from a demographically representative sample of 428 patients who had completed NECT scans following hospitalisation for stroke. In a subset of the scans (n = 20), the intracranial spaces were segmented using automated tools and compared to the gold standard of manual delineation to calculate accuracy, precision, recall, and dice similarity coefficient (DSC) values. Further, three readers independently performed regional visual comparisons of the quality of the results in a larger dataset (n = 428). Three tools were found; one of these had unreliable performance so subsequent evaluation was discontinued. The remaining tools included one that was adapted from the FMRIB software library (fBET) and a convolutional neural network- based tool (rBET). Quantitative comparison showed comparable accuracy, precision, recall and DSC values (fBET: 0.984 ± 0.002; rBET: 0.984 ± 0.003; p = 0.99) between the tools; however, intracranial volume was overestimated. Visual comparisons identified characteristic regional differences in the resulting cranial cavity segmentations. Overall fBET had highest visual quality ratings and was preferred by the readers in the majority of subject results (84%). However, both tools produced high quality extractions of the intracranial space and our findings should improve confidence in these automated CT tools. Pre- and post-processing techniques may further improve these results.

Characterisation of the immune microenvironment of primary breast cancer and brain metastasis reveals depleted T-cell response associated to ARG2 expression.

BACKGROUND: Immune checkpoint inhibition is an established treatment in programmed death-ligand 1 (PD-L1)-positive metastatic triple-negative (TN) breast cancer (BC). However, the immune landscape of breast cancer brain metastasis (BCBM) remains poorly defined. MATERIALS AND METHODS: The tumour-infiltrating lymphocytes (TILs) and the messenger RNA (mRNA) levels of 770 immune-related genes (NanoString™, nCounter™ Immuno-oncology IO360) were assessed in primary BCs and BCBMs. The prognostic role of ARG2 transcripts and protein expression in primary BCs and its association with outcome was determined. RESULTS: There was a significant reduction of TILs in the BCBMs in comparison to primary BCs. 11.5% of BCs presented a high immune infiltrate (hot), 46.2% were altered (immunosuppressed/excluded) and 34.6% were cold (no/low immune infiltrate). 3.8% of BCBMs were hot, 23.1% altered and 73.1% cold. One hundred and twelve immune-related genes including PD-L1 and CTLA4 were decreased in BCBM compared to the primary BCs (false discovery rate <0.01, log2 fold-change >1.5). These genes are involved in matrix remodelling and metastasis, cytokine-chemokine signalling, lymphoid compartment, antigen presentation and immune cell adhesion and migration. Immuno-modulators such as PD-L1 (CD274), CTLA4, TIGIT and CD276 (B7H3) were decreased in BCBMs. However, PD-L1 and CTLA4 expression was significantly higher in TN BCBMs (P = 0.01), with CTLA4 expression also high in human epidermal growth factor receptor 2-positive (P < 0.01) compared to estrogen receptor-positive BCBMs. ARG2 was one of four genes up-regulated in BCBMs. High ARG2 mRNA expression in primary BCs was associated with worse distant metastasis-free survival (P = 0.038), while ARG2 protein expression was associated with worse breast-brain metastasis-free (P = 0.027) and overall survival (P = 0.019). High transcript levels of ARG2 correlated to low levels of cytotoxic and T cells in both BC and BCBM (P < 0.01). CONCLUSION: This study highlights the immunological differences between primary BCs and BCBMs and the potential importance of ARG2 expression in T-cell depletion and clinical outcome.

Lesion probability mapping to explain clinical deficits and cognitive performance in multiple sclerosis.

BACKGROUND: Lesion dissemination in time and space represents a key feature and diagnostic marker of multiple sclerosis (MS). The correlation between magnetic resonance imaging (MRI) lesion load and disability is only modest, however. Strategic lesion location might at least partially account for this 'clinico-radiologic paradox'. OBJECTIVES: Here we used a non-parametric permutation-based approach to map lesion location probability based on MS lesions identified on T2-weighted MRI. We studied 121 patients with clinically isolated syndrome, relapsing-remitting or secondary progressive MS and correlated these maps to assessments of neurologic and cognitive functions. RESULTS: The Expanded Disability Status Scale correlated with bilateral periventricular lesion location (LL), and sensory and coordination functional system deficits correlated with lesion accumulation in distinct anatomically plausible regions, i.e. thalamus and middle cerebellar peduncule. Regarding cognitive performance, decreased verbal fluency correlated with left parietal LL comprising the putative superior longitudinal fascicle. Delayed spatial recall correlated with _amygdalar, _left frontal and parietal LL. Delayed selective reminding correlated with bilateral frontal and temporal LL. However, only part of the spectrum of cognitive and neurological problems encountered in our cohort could be explained by specific lesion location. CONCLUSIONS: Lesion probability mapping supports the association of specific lesion locations with symptom development in MS, but only to limited extent.

Chlorhexidine dressings could reduce external ventricular drain infections: results from a systematic review and meta-analysis.

The incidence of external ventricular drain (EVD) infections remains high. Chlorhexidine dressings have demonstrated efficacy in reducing infections associated with indwelling catheters at other body sites, although evidence for their use with EVDs is limited. The aim of this systematic review and meta-analysis was to evaluate the efficacy of chlorhexidine dressings in reducing EVD-associated cerebrospinal fluid infection (EVDAI). MEDLINE, EMBASE and the Cochrane library were queried for articles from inception. The primary outcome was the incidence of EVDAI. Secondary outcomes included device safety, microbiological outcomes and shunt-dependency. From 896 unique records, five studies were included of which four presented suitable data for quantitative analysis including three case series and one underpowered randomized controlled trial. There was a high risk of bias in all studies. A total of 880 patients were included with a mean age of 57.7 years (95% confidence interval (CI) 57.4-58.0 years). In primary outcome analysis, the chlorhexidine dressing group had a significantly lower incidence of EVDAI (1.7% vs 7.9%, risk difference (RD) = 0.07, 95% CI 0.00-0.13, P=0.04). In conclusion, chlorhexidine dressings may reduce the incidence of EVDAI but require future study in randomized trials to definitively determine efficacy.

Brain surface contraction mapped in first-episode schizophrenia: a longitudinal magnetic resonance imaging study.

Schizophrenia is associated with structural brain abnormalities, but the timing of onset and course of these changes remains unclear. Longitudinal magnetic resonance imaging (MRI) studies have demonstrated progressive brain volume decreases in patients around and after the onset of illness, although considerable discrepancies exist regarding which brain regions are affected. The anatomical pattern of these progressive changes in schizophrenia is largely unknown. In this study, MRI scans were acquired repeatedly from 16 schizophrenia patients approximately 2 years apart following their first episode of illness, and also from 14 age-matched healthy subjects. Cortical Pattern Matching, in combination with Structural Image Evaluation, using Normalisation, of Atrophy, was applied to compare the rates of cortical surface contraction between patients and controls. Surface contraction in the dorsal surfaces of the frontal lobe was significantly greater in patients with first-episode schizophrenia (FESZ) compared with healthy controls. Overall, brain surface contraction in patients and healthy controls showed similar anatomical patterns, with that of the former group exaggerated in magnitude across the entire brain surface. That the pattern of structural change in the early course of schizophrenia corresponds so closely to that associated with normal development is consistent with the hypothesis that a schizophrenia-related factor interacts with normal adolescent brain developmental processes in the pathophysiology of schizophrenia. The exaggerated progressive changes seen in patients with schizophrenia may reflect an increased rate of synaptic pruning, resulting in excessive loss of neuronal connectivity, as predicted by the late neurodevelopmental hypothesis of the illness.

Brain biopsy in the management of neurology patients.

BACKGROUND AND METHODS: To evaluate the value of brain biopsy for neurology patients in our unit, we conducted a retrospective audit of neurology patients referred for brain biopsies for non-neoplastic disease from 1993 to 2007. RESULTS: 64 patients [median (range) age 51 (16-74) years] were included. The clinical presentation was diffuse encephalopathy for 40 patients, focal for 13 and multifocal for 11. The biopsy was diagnostic in 34 patients, abnormal but non-diagnostic in 21 and normal in 9. There was a statistically significant association between clinical presentation and biopsy result (p = 0.004); diagnostic biopsies were more common in patients with focal or multifocal clinical presentations. Twenty patients (31%) had alterations of management as a result of their brain biopsy, comprising specific treatment (11 patients) or prognosis/diagnosis of untreatable conditions (9 patients). Diagnoses of treatable conditions included Whipple's disease, tuberculoma, progressive multifocal leukoencephalopathy, and neurosarcoidosis. Five patients (7.8%) had complications. CONCLUSIONS: Brain biopsy is useful and relatively safe in the management of neurology patients, with a diagnostic yield of 53% in our series; some led to significant changes in management, including treatment of infections. Patients with focal or multifocal presentation are more likely to yield a diagnostic biopsy result.

Using diffusion tensor imaging to detect cortical changes in fronto-temporal dementia subtypes.

Fronto-temporal dementia (FTD) is a common type of presenile dementia, characterized by a heterogeneous clinical presentation that includes three main subtypes: behavioural-variant FTD, non-fluent/agrammatic variant primary progressive aphasia and semantic variant PPA. To better understand the FTD subtypes and develop more specific treatments, correct diagnosis is essential. This study aimed to test the discrimination power of a novel set of cortical Diffusion Tensor Imaging measures (DTI), on FTD subtypes. A total of 96 subjects with FTD and 84 healthy subjects (HS) were included in the study. A "selection cohort" was used to determine the set of features (measurements) and to use them to select the "best" machine learning classifier from a range of seven main models. The selected classifier was trained on a "training cohort" and tested on a third cohort ("test cohort"). The classifier was used to assess the classification power for binary (HS vs. FTD), and multiclass (HS and FTD subtypes) classification problems. In the binary classification, one of the new DTI features obtained the highest accuracy (85%) as a single feature, and when it was combined with other DTI features and two other common clinical measures (grey matter fraction and MMSE), obtained an accuracy of 88%. The new DTI features can distinguish between HS and FTD subgroups with an accuracy of 76%. These results suggest that DTI measures could support differential diagnosis in a clinical setting, potentially improve efficacy of new innovative drug treatments through effective patient selection, stratification and measurement of outcomes.

Spinal cord tracts and clinical correlates.

The spinal cord tracts and common clinical presentations are tested along with spinal cord vasculature.

The role of the corpus callosum in seizure spread: MRI lesion mapping in oligodendrogliomas.

BACKGROUND: Some patients with oligodendrogliomas have generalized tonic-clonic seizures (GTCS) while others have only partial seizures (PS). We investigated the relationship between tumour localization and seizure generalization using quantitative lesion mapping on magnetic resonance images. METHODS: Twenty one patients with histologically proven oligodendrogliomas and GTCS (n=11) or PS (n=10) were studied. Data were acquired on a 3 Tesla MRI System. We performed lesion mapping techniques to compare the spatial distribution of oligodendrogliomas between patient groups, and quantitatively determined the extent to which lesions intersected each probabilistic regions-of-interest, including the cerebral lobes, thalamus, striatum, and genu of the corpus callosum. RESULTS: In patients experiencing GTCS, the greatest lesion load was observed in mesial frontal regions, including cortex connected to the genu. In contrast, the greatest lesion load in patients experiencing PS was observed more caudo-laterally in orbitofrontal and temporal lobes, but typically sparing cortex connected to the genu. The number of lesion intersections with genu region of interest was significantly greater in patients experiencing GTCS relative to patients with PS (p=0.03). There were no significant differences between patient groups with respect to lesion intersection with the individual cerebral lobes, thalamus and striatum, or with respect to overall oligodendroglioma size. CONCLUSION: Our data suggest that the genu of the corpus callosum may be a major pathway for seizure generalization in patients with oligodendrogliomas.

Synaesthesia in the normal limb.

We explored the degree to which vision may alter kinaesthetic perception by asking participants to view their hand through a prism, introducing different horizontal deviations, while trying to align their fingers above and below a thin table. When the visual image of one hand was displaced this overwhelmed kinaesthetic judgements and participants reliably reported that they felt their limbs were aligned, even when they were laterally mis-aligned by as much as 10 cm. This effect, however, was mediated by 'visual capture' and when the task was attempted in a darkened room with limb position indicated by an LED taped to the finger, kinaesthesis dominated and participants reported that the LED seemed to become detached from their finger tip. In both light and dark conditions the finger was clearly visible and only the background detail was extinguished. Hence, in perceiving limb position, it appears that we believe in what we see, rather than in what we feel, when the visual background is rich, and in what we feel when the visual background is sparse.

White matter and lesion T1 relaxation times increase in parallel and correlate with disability in multiple sclerosis.

Previous studies have established the clinical relevance of hypointense lesions ("black holes") on T1-weighted MRI as a surrogate marker for pathological change [36]. In contrast to measuring the volume of "black holes", the direct measurement of T1 values allows an objective assessment of the changes contributing to hypointensity both in the focal lesions and in the normal appearing white matter (NAWM). The aims of this study were first, to determine the relationship between T1 values in the NAWM and in discrete lesions, second, to test the relationship between white matter T1 changes and measures of disability and third, to determine whether pathology leading to T1 change occurred in thalamic grey matter of patients with multiple sclerosis. 24 patients with clinically definite multiple sclerosis (13 with relapsing-remitting multiple sclerosis and 11 with secondary progressive multiple sclerosis) and 11 controls participated. White matter T1 histograms and mean T1 values for the thalamus were generated from whole brain T1 relaxation time maps measured using a novel echo-planar imaging based MRI sequence at 3Tesla. Tissue segmentation based on T2- and T1-weighted images allowed independent study of changes in lesions and NAWM. White matter T1 histograms from the patient group showed a reduced peak height and a shift towards higher T1 values (p = 0.028) relative to controls. The mean thalamic T1 was greater for secondary progressive patients than for healthy controls (p = 0.03). Mean white matter T1 values correlated significantly with disability (r = 0.48, p = 0.02). The mean T1 value in the T1-hypointense lesions correlated strongly with the mean T1 value in the NAWM (r = 0.80, p < 0.001). No significant relationship was found between mean white matter T1 value and cerebral volume (r = -0.23, p = 0.31). The T1 measurements extend previous observations suggesting that changes in the NAWM occur in parallel with pathology in lesions of MS. T1 measurements of either the total or NAWM therefore may provide a potentially observer- and scanner- independent marker of pathology relevant to disability in MS.

MRI brain T1 relaxation time changes in MS patients increase over time in both the white matter and the cortex.

OBJECTIVE: To test the sensitivity of whole-brain T1 relaxometry to the evolution of pathological changes in multiple sclerosis (MS). BACKGROUND: T1-weighted hypointense lesion load in the brains of patients with MS is associated with axonal loss. Other work has shown that T1 measurements may provide information complementary to existing imaging techniques, such as magnetization transfer imaging. METHODS: The authors studied 14 MS patients twice over a median time interval of 19.5 months (range, 14-22 months). Structural images and whole-brain T1 maps using a novel rapid-scanning technique (3 min/study) were performed at 3 T. Analysis focused on defining changes separately in the lesional and normal-appearing white matter (NAWM) and in the cortical gray matter. RESULTS: At baseline, there was an inverse relationship between disease duration and the NAWM T1 histogram peak height (r = -0.75, P = .03). The total white matter T1 histogram peak height decreased over time (P < .001). This could be accounted for by changes in the NAWM (P < .03). There also was a decrease (6%) in the mean (11 of 14 patients, P = .004) and in the median (7%) (13 of 14 patients, P < .001) neocortical gray matter T1 over the follow-up period. CONCLUSIONS: Brain T1 maps can be generated quickly and are sensitive to pathological changes over time. T1 values in both the gray and the white matter at the baseline visit were related to disease duration, suggesting that the T1 changes are clinically relevant. Although the absolute values will be different, it is likely that similar changes will be able to be detected at 1.5 T. The role of T1 measurement as a magnetic resonance imaging outcome measure in clinical trials now should be explored.