Incidental White Matter Research Articles

Mortality Outcomes in a Large Population with and without Covert Cerebrovascular Disease.

Covert cerebrovascular disease (CCD) is frequently reported on neuroimaging and associates with increased dementia and stroke risk. We aimed to determine how incidentally-discovered CCD during clinical neuroimaging in a large population associates with mortality. We screened CT and MRI reports of adults aged ≥50 in the Kaiser Permanente Southern California health system who underwent neuroimaging for a non-stroke clinical indication from 2009-2019. Natural language processing identified incidental covert brain infarcts (CBI) and/or white matter hyperintensities (WMH), grading WMH as mild/moderate/severe. Models adjusted for age, sex, ethnicity, multimorbidity, vascular risks, depression, exercise, and imaging modality. Of n=241,028, the mean age was 64.9 (SD=10.4); mean follow-up 4.46 years; 178,554 (74.1%) had CT; 62,474 (25.9%) had MRI; 11,328 (4.7%) had CBI; and 69,927 (29.0%) had WMH. The mortality rate per 1,000 person-years with CBI was 59.0 (95%CI 57.0-61.1); with WMH=46.5 (45.7-47.2); with neither=17.4 (17.1-17.7). In adjusted models, mortality risk associated with CBI was modified by age, e.g. HR 1.34 [1.21-1.48] at age 56.1 years vs HR 1.22 [1.17-1.28] at age 72 years. Mortality associated with WMH was modified by both age and imaging modality e.g., WMH on MRI at age 56.1 HR = 1.26 [1.18-1.35]; WMH on MRI at age 72 HR 1.15 [1.09-1.21]; WMH on CT at age 56.1 HR 1.41 [1.33-1.50]; WMH on CT at age 72 HR 1.28 [1.24-1.32], vs. patients without CBI or without WMH, respectively. Increasing WMH severity associated with higher mortality, e.g. mild WMH on MRI had adjusted HR=1.13 [1.06-1.20] while severe WMH on CT had HR=1.45 [1.33-1.59]. Incidentally-detected CBI and WMH on population-based clinical neuroimaging can predict higher mortality rates. We need treatments and healthcare planning for individuals with CCD.

Incidental white matter hyperintensities on magnetic resonance imaging - are they clinically important?

Incidental white matter hyperintensities on magnetic resonance imaging - are they clinically important?

An observational study of T2-weighted white matter hyperintensities on magnetic resonance imaging of the internal auditory meatus and brain: ignore or not?

Magnetic resonance imaging of the internal auditory meatus frequently detects incidental white matter hyperintensities. This study investigated the association between these and the risk of stroke and transient ischaemic attack, or myocardial infarction. The records of patients with incidental white matter hyperintensities were reviewed, and data were collected on: age, sex, cardiovascular risk factors, and incidence of stroke and transient ischaemic attack, or myocardial infarction, five years later. The risk factors associated with vascular events were explored. Of 6978 patients, 309 (4.4 per cent) had incidental white matter hyperintensities. Of these, 20 (6.5 per cent) had a stroke or transient ischaemic attack within five years, and 5 (1.7 per cent) had a myocardial infarction. The number of cardiovascular risk factors was significantly associated with the incidence of stroke and transient ischaemic attack (p = 0.004), and myocardial infarction (p = 0.023). The number of cardiovascular risk factors predicts the likelihood of vascular events; appropriate risk factor management is recommended for patients with incidental white matter hyperintensities of presumed vascular origin.

Elevated Circulating Microparticle Subpopulations in Incidental Cerebral White Matter Hyperintensities: A Multimodal Study.

Asymptomatic (or “silent”) manifestations of cerebral small vessel disease (CSVD) are widely recognized through incidental findings of white matter hyperintensities (WMHs) as a result of magnetic resonance imaging (MRI). This study aims to examine the potential associations of surrogate markers for the evaluation of white matter integrity in CSVD among asymptomatic individuals through a battery of profiling involving QRISK2 cardiocerebrovascular risk prediction, neuroimaging, neurocognitive evaluation, and microparticles (MPs) titers. Sixty asymptomatic subjects (mean age: 39.83 ± 11.50 years) with low to moderate QRISK2 scores were recruited and underwent neurocognitive evaluation for memory and cognitive performance, peripheral venous blood collection for enumeration of selected MPs subpopulations, and 3T MRI brain scan with specific diffusion MRI (dMRI) sequences inclusive of diffusion tensor imaging (DTI). WMHs were detected in 20 subjects (33%). Older subjects (mean age: 46.00 ± 12.00 years) had higher WMHs prevalence, associated with higher QRISK2 score and reduced processing speed. They also had significantly higher mean percentage of platelet (CD62P)- and leukocyte (CD62L)-derived MPs. No association was found between reduced white matter integrity—especially at the left superior longitudinal fasciculus (LSLF)—with age and neurocognitive function; however, LSLF was associated with higher QRISK2 score, total MPs, and CD62L- and endothelial cell-derived MPs (CD146). Therefore, this study establishes these multimodal associations as potential surrogate markers for “silent” CSVD manifestations in the well-characterized cardiocerebrovascular demographic of relatively young, neurologically asymptomatic adults. Furthermore, to the best of our knowledge, this study is the first to exhibit elevated MP counts in asymptomatic CSVD (i.e., CD62P and CD62L), which warrants further delineation.

Cognitive and balance impairments in people with incidental white matter hyperintensities

BackgroundWhite matter hyperintensities (WMHs) is the most frequent type of cerebral small vessel diseases and a common incidental finding in MRI films of the geriatric population. The objectives of this work were to study the existence of occult cognitive and balance impairments in subjects with accidentally discovered WMHs.MethodsThe study was conducted on 44 subjects with accidentally discovered WMHs and 24 non-WMHs subjects submitted to the advanced activity of daily living scale (AADLs), a neurocognitive battery assessing different cognitive domains, Berg balance test (BBT), computerized dynamic posturography (CDP), and brain MRI diffusion tensor tractography (DTT).ResultsWMHs subjects showed a significant decrease in AADLs as well as visual and vestibular ratios of CDP. Regarding the neurocognitive battery, there were significant decreases in MoCA as well as arithmetic test and block design of Wechsler adult intelligence scale-IV in WMHs compared to non-WMHs subjects’ groups (p value < 0.001). Concerning Wisconsin Card Sorting subtests, each preservative response, preservative errors, non-preservative errors and trials to complete the 1st category showed a highly significant increase in WMHs compared to non-WMHs subjects (p values < 0.001). DTT showed a substantial reduction in fractional anisotropy (FA) of each corticospinal tract, thalamocortical connectivity, and arcuate fasciculi.ConclusionSubjects with WMHs have lower cognitive performance and subtle balance impairment which greatly impair their ADLs.

Longitudinal relaxographic imaging of white matter hyperintensities in the elderly.

BackgroundIncidental white matter hyperintensities (WMHs) are common findings on T2-weighted magnetic resonance images of the aged brain and have been associated with cognitive decline. While a variety of pathogenic mechanisms have been proposed, the origin of WMHs and the extent to which lesions in the deep and periventricular white matter reflect distinct etiologies remains unclear. Our aim was to quantify the fractional blood volume (vb) of small WMHs in vivo using a novel magnetic resonance imaging (MRI) approach and examine the contribution of blood–brain barrier disturbances to WMH formation in the deep and periventricular white matter.MethodsTwenty-three elderly volunteers (aged 59–82 years) underwent 7 Tesla relaxographic imaging and fluid-attenuated inversion recovery (FLAIR) MRI. Maps of longitudinal relaxation rate constant (R1) were prepared before contrast reagent (CR) injection and throughout CR washout. Voxelwise estimates of vb were determined by fitting temporal changes in R1 values to a two-site model that incorporates the effects of transendothelial water exchange. Average vb values in deep and periventricular WMHs were determined after semi-automated segmentation of FLAIR images. Ventricular permeability was estimated from the change in CSF R1 values during CR washout.ResultsIn the absence of CR, the total water fraction in both deep and periventricular WMHs was increased compared to normal appearing white matter (NAWM). The vb of deep WMHs was 1.8 ± 0.6 mL/100 g and was significantly reduced compared to NAWM (2.4 ± 0.8 mL/100 g). In contrast, the vb of periventricular WMHs was unchanged compared to NAWM, decreased with ventricular volume and showed a positive association with ventricular permeability.ConclusionsHyperintensities in the deep WM appear to be driven by vascular compromise, while those in the periventricular WM are most likely the result of a compromised ependyma in which the small vessels remain relatively intact. These findings support varying contributions of blood–brain barrier and brain-CSF interface disturbances in the pathophysiology of deep and periventricular WMHs in the aged human brain.

Tumefactive Virchow-Robin spaces: A rare cause of obstructive hydrocephalus.

A middle-aged male presented with complaints of mild headache and unsteadiness of gait for past 2 years. His physical examination and lab results, including the cerebrospinal fluid (CSF) examination were unremarkable. Magnetic resonance imaging (MRI) of brain was done which revealed a cluster of cysts in the midbrain isointense to CSF on all sequences [Figures 1 and 2]. No enhancement of the cyst walls was seen on post-gadolinium images [Figure 3]. MR spectroscopy did not show any choline, lipid, or amino acid peak in the lesions. These were seen to cause mass effect on aqueduct of Sylvius and mild obstructive hydrocephalus. Review of MRI done before 2 years revealed the same lesions in the mesencephalothalamic region; no change in size or signal intensity was observed in the present scan. The final diagnosis was tumefactive Virchow-Robin spaces causing mild hydrocephalus. The patient was referred to neurosurgery department for further management. A VP shunt was placed with dramatic resolution of symptoms.Figure 1: Axial T1-weighted images show cluster of cysts in the mesencephalic region isointense to cerebrospinal fluid (CSF)Figure 2: Coronal fluid attenuated inversion recovery (FLAIR) image shows CSF isointense cysts in mesencephalothalamic region causing mild hydrocephalus. Periventricular hyperintense signal is due to transependymal seepage and/or microvascular ischemiaFigure 3: Coronal post-gadolinium T1-weighted images do not reveal any enhancement of cysts, consistent with the diagnosis of tumefactive perivascular spacesThe Virchow-Robin or perivascular spaces are pial-lined, fluid-filled spaces accompanying perforating arteries and venules. Typical perivascular spaces occur along lenticulostriate arteries above the anterior perforating substance and anterior commissure. They may occur less commonly in subcortical location, subinsular region, and cerebellum.[1] Rarely they may become enlarged (called tumefactive Virchow-Robin spaces) and cause mass effect and hydrocephalus (especially those found in mesencephalothalamic region); these need to be distinguished from cystic neoplasms.[2] Some authors have proposed the term Virchoma for enlarged mesencephalic perivascular spaces.[3] Tumefactive or cavernous dilation of Virchow-Robin spaces occurring in mesencephalothalamic region may be associated with hydrocephalus. The diagnostic features for tumefactive or cavernous dilation of Virchow-Robin spaces in this case are, an absence of signal from the lesion on the fluid attenuated inversion recovery (FLAIR) imaging, no abnormal signal in the adjacent neuroparenchyma, no contrast enhancement on post-gadolinium scans, and no change in size or appearance over 2 years. The differential diagnosis of tumefactive perivascular spaces includes cystic neoplasms, parasitic cysts, ventricular diverticulae, nonneoplastic neuroepithelial cysts, and mucopolysaccharidosis.[345] Extreme unilateral dilation of Virchow-Robin spaces may also be encountered.[6] Large Virchow-Robin spaces (VRS) have been associated with age, dementia, multiple sclerosis, trauma, hypertension, and incidental white matter lesions.[178] Surgical shunting of the hydrocephalus associated with VR spaces has produced variable clinical results (with improvement in gait disturbances, bradykinesia, and urinary symptoms). We conclude that mesencephalic tumefactive Virchow Robin spaces can cause obstructive hydrocephalus, and rare manifestations of a common entity should always be considered.

Radiologically Isolated Syndrome: An Overview

The use of brain magnetic resonance imaging (MRI) for evaluation of neurological disorders has increased in the past two decades. This has led to an increased detection of incidental findings on brain MRI. The most common of these asymptomatic abnormalities are white matter lesions that are interpreted as demyelinating based on radiological criteria. However, in the absence of associated clinical symptoms suggestive of multiple sclerosis (MS), a definite diagnosis of MS cannot be made in patients with these incidental white matter lesions. These patients are now diagnosed as radiologically isolated syndrome (RIS). The natural history and clinical approach to patients with RIS are reviewed in this article.

Prevalence of white matter lesions and stroke in children with migraine

To determine the prevalence of white matter lesions (WMLs) and infarcts in children with migraine and whether pediatric migraine could be a risk factor for silent ischemic lesions or stroke. Prospectively collected data from 1,008 pediatric patients with headache were reviewed. The MRI data were collected and retrospectively reviewed. Of the 926 patients diagnosed with migraine, 375 patients had MRIs and 115 had abnormalities, of which 39 had WMLs. Among them, 24 (6% of migraine) patients had incidental white matter findings without known neurovascular disease, risk factors, or etiologies for WMLs. The prevalence of WMLs is more common in migraine with aura (10%) than without aura (4%) (p = 0.038), but it is not statistically significant compared with controls (4%) (p = 0.119). Deep WMLs are more prevalent than periventricular lesions; these are detected mainly in the frontal and parietal lobes. No lesions appeared to be infarct-like lesions. There was no association between the total lesion load and chronicity or the frequency of migraine. WMLs are nonprogressive. Pediatric migraineurs with aura do not develop stroke, based on the available follow-up data. WMLs in pediatric patients with migraine and aura are no more prevalent than in controls. They appear to be benign and are not associated with stroke.

O55 – 1566 Incidental white matter lesions in children presenting with headache

O55 – 1566 Incidental white matter lesions in children presenting with headache

Deterioration of Gait and Balance over Time: The Effects of Age-Related White Matter Change - The LADIS Study

Background: Cross-sectional studies have shown an association between the severity of age-related white matter change (ARWMC) and lower body motor function. However, the association between prevalent ARWMC and incident deterioration of balance and gait remains insufficiently investigated. This study investigates if the degree of prevalent ARWMC has a differential effect on lower body motor function as it changes over time, hypothesizing that individuals with more severe baseline white matter pathology experience greater clinical deterioration independent of potential confounders. This is of clinical relevance: given the increasing use of neuroimaging, incidental white matter pathology is common; being able to delineate natural trajectories of balance and gait function given ARWMC may improve patient advice and help optimize allocation of care. Methods: 639 non-disabled elderly individuals with prevalent ARWMC (grading of severity of ARWMC using the Fazekas scale) were followed up yearly for 3 years, as part of the Leukoaraiosis and Disability Study. The primary outcome variable, reflecting the temporal course of gait and balance function, was the change of scores on the Short Physical Performance Battery (SPPB) over time versus the severity of ARWMC. We used linear mixed modelling to analyse change over time. Explorative analysis was carried out investigating the effect of age on potential deterioration of gait and balance function. We used propensity scores to adjust for multiple confounders that affect both the exposure (i.e. ARWMC) and outcome. Results: Subjects' lower body motor function deteriorated by 2.6% per year. However, after adjustment for baseline motor impairment and potential confounders, only subjects with moderate [-0.22 points per year on the SPPB (equals -2.3%); 95% CI -0.35 to -0.09, p < 0.001] or severe [-0.46 points per year (equals -4.7%); 95% CI -0.63 to -0.28, p < 0.0001] ARWMC show a loss of function. Age shows differential effects: relatively younger elderly subjects have similar temporal dynamics in SPPB change independent of their individual degree of ARWMC severity; however, subjects with severe ARWMC and who are older than 75.9 years deteriorate significantly more rapidly than their counterparts with only mild or moderate white matter pathology. Conclusion: Only moderate and severe ARWMC is independently associated - on average - with a deterioration of gait and balance. Albeit the possibility of unmeasured confounding and other methodological constraints, there is nonetheless evidence of large interindividual variability: some subjects with moderate or severe ARWMC stay stable over time or even show improvement. Furthermore, there is explorative analysis showing that younger elderly subjects may be able to better compensate even severe ARWMC. These individuals' gait and balance function stays relatively stable over time, whereas their older counterparts deteriorate significantly. This may point towards a threshold effect given ARWMC.

Incidental White Matter Lesions in Children Presentıng With Headache

We aimed to describe the prevalence and significance of white matter lesions detected on magnetic resonance imaging (MRI) in children with headache. Children who were admitted with the complaint of headache and had neuroimaging between December 2007 and June 2012 were included in the study. The clinical and neuroimaging data of the patients were retrospectively evaluated. MRI results of the patients were documented in detail. The patients with non-specific white matter lesions were called for a control visit, and current status of headache and neurological findings were determined. A total of 941 patients were included in the study. Sixty-one percent of the patients received cranial neuroimaging. 8.2% had only cranial computed tomography (CT), 7.5% had cranial CT and cranial MRI, and 84.3% had only cranial MRI. 22.1% of the patients had abnormal cranial MRI findings. The rate of incidental non-specific white matter changes detected in our study group was 23/527 (4.4%). Among the 23 patients, 12 (52.2%) were male and 11 (47.8%) were female. Fourteen (60.9%) had migraine without aura, 8 (34.8%) had tension-type headache, and 1 (4.3%) had migraine with aura. Mean age of patients at the time of imaging was 12.1 ± 3.4 years (range 4.0-16.0 years). All patients with non-specific white matter changes on MRI showed normal psychomotor development, and there was no history of seizures or head trauma. The physical and neurological examinations of all patients were normal. The mean clinical follow-up period of the patients was 16.8 ± 17.3 months (range 6-80 months). No patients showed neurological deterioration during the follow up. The white matter lesions were supratentorial in all patients. The mean size of the lesions was 5.1 ± 4.5 mm (minimum, 2 mm; maximum, 24 mm). Repeated radiological evaluations were performed in 11 (47.8%) of the patients. No new white matter lesions were detected in control MRI during follow up. Non-specific incidental white matter changes may be seen in children with headache. For normal clinical follow up, in the absence of evident benefits from repeated imaging studies, we suggest that repeated imaging studies are not warranted in every patient and should be tailored according to clinical course.

Prevalence of brain magnetic resonance imaging meeting Barkhof and McDonald criteria for dissemination in space among headache patients

Background: Incidental T2 white matter hyperintensities (WMHs) in headache patients on brain magnetic resonance imaging (MRI) may prompt concern for demyelinating disease. Objective: We reviewed brain MRI studies in patients with headaches without known demyelinating disease to determine the prevalence meeting imaging criteria for multiple sclerosis (MS) using two different definitions of “juxtacortical” and “periventricular”. Methods: Consecutive patients undergoing pre- and post-contrast MRI for headaches over a 25-month period were retrospectively identified. Exclusions included patients under age 10 and over 55 years or with known demyelinating disorder. Patients were classified as meeting: 1) Barkhof and 2) 2010 McDonald dissemination in space criteria for MS based on: FLAIR/T2 scans for WMH and enhanced T1-weighted images for enhancement. Both groups were further differentiated by defining “periventricular” and “juxtacortical” as WMH contacting ventricle and cortex (Barkhof “touching”, McDonald “touching”) versus WMH within 3 mm (Barkhof – 3 mm, McDonald – 3 mm). Results: 326/564 (58%) studies met inclusion criteria. WMH prevalence was 168/326 (51.53%). Barkhof “touching” criteria were met in 4/168 (2.4%) and in 12/168 (7.1%) of the 3 mm group. McDonald criteria were met in 41/168 (24.4%) for “touching” and 58/168 (34.5%) for 3 mm, respectively. Conclusion: Barkhof and McDonald criteria were met in 2.4–7.1% and 24.4–34.5%, respectively.

Brain imaging in normal kids: a community‐based MRI study in Malawian children

To collect normative MRI data for effective clinical and research applications. Such data may also offer insights into common neurological insults. We identified a representative, community-based sample of children aged 9-14years. Children were screened for neurodevelopmental problems. Demographic data, medical history and environmental exposures were ascertained. Eligible children underwent the Neurologic Examination for Subtle Signs (NESS) and a brain MRI. Descriptive findings and analyses to identify risk factors for MRI abnormalities are detailed. One hundred and two of 170 households screened had age-appropriate children. Two of 102 children had neurological problems - one each with cerebral palsy and epilepsy. Ninety-six of 100 eligible children were enrolled. Mean age was 11.9years (SD 1.5), and 43 (45%) were boys. No acute MRI abnormalities were seen. NESS abnormalities were identified in 6 of 96 children (6%). Radiographic evidence of sinusitis in 29 children (30%) was the most common MRI finding. Brain abnormalities were found in 16 (23%): mild diffuse atrophy in 4 (4%), periventricular white matter changes/gliosis in 6 (6%), multifocal punctuate subcortical white matter changes in 2 (2%), vermian atrophy in 1 (1%), empty sella in 3 (3%) and multifocal granulomas with surrounding gliosis in 1 (1%). Having an abnormal MRI was not associated with age, sex, antenatal problems, early malnutrition, febrile seizures, an abnormal neurological examination or housing quality (all P values >0.05). No predictors of radiographic sinusitis were identified. Incidental brain MRI abnormalities are common in normal Malawian children. The incidental atrophy and white matter abnormalities seen in this African population have not been reported among incidental findings from US populations, suggesting Malawi-specific exposures may be the cause.

Incidental Multifocal White Matter Lesions in Pediatric Magnetic Resonance Imaging

This study sought to describe the occurrence and potential significance of white matter abnormalities of unknown cause on pediatric cranial magnetic resonance scans, and to review the literature. We included 16 children in whom white matter abnormalities were incidentally revealed on magnetic resonance scans performed during a 7-year period at a tertiary pediatric medical center. Background data were retrospectively collected from medical files. White matter lesions were classified by size, location, and extent. Indications for imaging included convulsive disorder (n = 5), headache (n = 5), endocrine disorder (n = 4), and others. Patients' abnormalities did not correlate with the locations and patterns of white matter lesions. No changes in lesions were evident over time. Given the absence of evident benefits from repeated imaging studies, we suggest they are not warranted in every patient, and should be tailored according to clinical course. Further investigations of incidental intracranial findings are required in this age group.

140 Pilot MRI study of white matter changes in rheumatoid patients who have had anti-TNFα therapy

ObjectivesTo compare the magnetisation transfer ratio (MTR) and volume of incidental white matter (WM) lesions of patients who have had anti-tumour necrosis factor-α (TNFα) therapy to that of healthy controls,...

HFE H63D, C282Y and AGTR1 A1166C Polymorphisms and Brain White Matter Lesions in the Aging Brain

: Incidental white matter lesions (WML) are a common neuroradiological finding in elderly people and have been linked to dementia and depression. Various mechanisms including hypoxia and increased production of reactive oxygen species (ROS) are implicated in the etiology of WML. The hemochromatosis (HFE) gene p.H63D and p.C282Y polymorphisms have been linked to dysregulation of iron metabolism and increased levels of ROS, whereas Angiotensin II receptor 1 (AGTR1) c.1166A → C polymorphism is known as a vascular risk factor. These genetic polymorphisms were characterized in brains donated to the UK MRC Cognitive Function and Ageing Study (CFAS) to assess their potential role in the risk for development of age-related WML. The study cohort comprised 258 brain donated to CFAS. WML severity was assessed in the postmortem brain donations using magnetic resonance imaging (MRI) scans and scored using the Scheltens’ scale. Polymerase chain reaction (PCR) amplification of extracted DNA followed by restriction enzyme digestion was used to genotype the samples. Genotypes were validated using direct sequencing in a smaller sample. The results show that HFE p.H63D polymorphism is not associated with WML severity in the whole cohort. However, there is a significant association of the D allele with severity of WML in noncarriers of the APOE ε4 allele. No association is demonstrated between the HFE p.C282Y nor the AGTR1 c.1166A → C polymorphisms and WML severity. The HFE gene appears to be a genetic risk factor for severe aging WML independently of the APOE ε4 genotype. This would support the role of iron-related oxidative stress, in addition to previously studied factors, e.g., hypoxia as potential risk factors for developing prominent aging WML.

04 Direct access to brain MR imaging for headache in primary care; better than an Aspirin?

In an attempt to demand manage the inexorable annual increase in neurology referrals our PCT introduced direct access to brain MRI for GPs in 2009. It was predicted that this...

Lesion Explorer: A comprehensive segmentation and parcellation package to obtain regional volumetrics for subcortical hyperintensities and intracranial tissue

Subcortical hyperintensities (SH) are a commonly observed phenomenon on MRI of the aging brain (Kertesz et al., 1988). Conflicting behavioral, cognitive and pathological associations reported in the literature underline the need to develop an intracranial volumetric analysis technique to elucidate pathophysiological origins of SH in Alzheimer's disease (AD), vascular cognitive impairment (VCI) and normal aging (De Leeuw et al., 2001; Mayer and Kier, 1991; Pantoni and Garcia, 1997; Sachdev et al., 2008). The challenge is to develop processing tools that effectively and reliably quantify subcortical small vessel disease in the context of brain tissue compartments. Segmentation and brain region parcellation should account for SH subtypes which are often classified as: periventricular (pvSH) and deep white (dwSH), incidental white matter disease or lacunar infarcts and Virchow–Robin spaces. Lesion Explorer (LE) was developed as the final component of a comprehensive volumetric segmentation and parcellation image processing stream built upon previously published methods (Dade et al., 2004; Kovacevic et al., 2002). Inter-rater and inter-method reliability was accomplished both globally and regionally. Volumetric analysis showed high inter-rater reliability both globally (ICC=.99) and regionally (ICC=.98). Pixel-wise spatial congruence was also high (SI=.97). Whole brain pvSH volumes yielded high inter-rater reliability (ICC=.99). Volumetric analysis against an alternative kNN segmentation revealed high inter-method reliability (ICC=.97). Comparison with visual rating scales showed high significant correlations (ARWMC: r=.86; CHIPS: r=.87). The pipeline yields a comprehensive and reliable individualized volumetric profile for subcortical vasculopathy that includes regionalized (26 brain regions) measures for: GM, WM, sCSF, vCSF, lacunar and non-lacunar pvSH and dwSH.

Incidental MRI anomalies suggestive of multiple sclerosis

The discovery and broad application of MRI in medicine has led to an increased awareness in the number of patients with incidental white matter pathology in the CNS. Routinely encountered in clinical practice, the natural history or evolution of such individuals with respect to their risk of developing multiple sclerosis (MS) is unclear. To investigate the natural history of patients who exhibit incidental imaging findings highly suggestive of MS pathology. Detailed clinical and radiologic data were obtained from asymptomatic patients with MRI anomalies suggestive of MS. The cohort consisted of 41 female and 3 male subjects (median age = 38.5, range: 16.2-67.1). Clinical evaluations were performed in 44 patients at the time of initial imaging; longitudinal clinical follow-up occurred for 30 patients, and longitudinal MRI data were acquired for 41 patients. Neurologic examination at the time of the initial MRI scans was normal in nearly all cases. While radiologic progression was identified in 59% of cases, only 10 patients converted to either clinically isolated syndrome or definite MS. The presence of contrast-enhancing lesions on the initial MRI was predictive of dissemination in time on repeat imaging of the brain (hazard ratio [HR] = 3.4, 95% confidence interval [1.3, 8.7], p = 0.01). Individuals with MRI anomalies highly suggestive of demyelinating pathology, not better accounted for by another disease process, are very likely to experience subsequent radiologic or clinical events related to multiple sclerosis. Additional studies will be necessary to fully define this risk.