Changes In White Matter Lesions Research Articles

Evolution of radiation-induced temporal lobe injury after intensity-modulated radiation therapy in nasopharyngeal carcinoma: a large cohort retrospective study

BackgroundPrevious studies have demonstrated conflicting findings regarding the initial MRI patterns of radiotherapy-induced temporal lobe injury (RTLI) and the evolution of different RTLI patterns. The aim of this study was to evaluate the initial MRI pattern and evolution of RTLI in patients with nasopharyngeal carcinoma (NPC) by means of a large cohort study.MethodsData of patients with RTLI were retrospectively collected from two hospitals between January 2011 and December 2021. The injured lobes were categorized into three patterns based on initial MRI patterns: isolated white matter lesions (WMLs), isolated contrast-enhanced lesions (CELs), and combined WMLs and CELs. The latency period, MRI appearances, and temporal changes in WMLs and CELs were evaluated.ResultsA total of 913 RTLI patients with 1092 injured lobes were included in this study. The numbers of isolated WMLs, isolated CELs, and combined WMLs and CELs identified at the first MRI detection were 7 (0.6%), 172 (15.8%), and 913 (83.6%), respectively. The evolution of bilateral RTLI was different in the same patient, and that of unilateral RTLI combined with WMLs and CELs also may occur asynchronously. The time intervals from the initial MRI detection of isolated WMLs, isolated CELs, combined WMLs and CELs to the last negative MRI scan were 8.6, 8.9 and 11.0 months, respectively. A significant difference was observed in the time intervals between the three patterns (H = 14.287, P = 0.001). And the time interval was identified as an independent factor influencing the initial MRI pattern of RTLI after Poisson regression (P = 0.002).ConclusionBoth WMLs and CELs could be the initial and only MRI abnormalities in patients with RTLI. This study is of great significance in accurately diagnosing RTLI early and providing timely treatment options. Additionally, it provides clinical evidence for guidelines on NPC, emphasizing the importance of regular follow-up of NPC patients.

Association of Intensive vs Standard Blood Pressure Control With Regional Changes in Cerebral Small Vessel Disease Biomarkers

Little is known about the associations of strict blood pressure (BP) control with microstructural changes in small vessel disease markers. To investigate the regional associations of intensive vs standard BP control with small vessel disease biomarkers, such as white matter lesions (WMLs), fractional anisotropy (FA), mean diffusivity (MD), and cerebral blood flow (CBF). The Systolic Blood Pressure Intervention Trial (SPRINT) is a multicenter randomized clinical trial that compared intensive systolic BP (SBP) control (SBP target <120 mm Hg) vs standard control (SBP target <140 mm Hg) among participants aged 50 years or older with hypertension and without diabetes or a history of stroke. The study began randomization on November 8, 2010, and stopped July 1, 2016, with a follow-up duration of approximately 4 years. A total of 670 and 458 participants completed brain magnetic resonance imaging at baseline and follow-up, respectively, and comprise the cohort for this post hoc analysis. Statistical analyses for this post hoc analysis were performed between August 2020 and October 2022. At baseline, 355 participants received intensive SBP treatment and 315 participants received standard SBP treatment. The main outcomes were regional changes in WMLs, FA, MD (in white matter regions of interest), and CBF (in gray matter regions of interest). At baseline, 355 participants (mean [SD] age, 67.7 [8.0] years; 200 men [56.3%]) received intensive BP treatment and 315 participants (mean [SD] age, 67.0 [8.4] years; 199 men [63.2%]) received standard BP treatment. Intensive treatment was associated with smaller mean increases in WML volume compared with standard treatment (644.5 mm3 vs 1258.1 mm3). The smaller mean increases were observed specifically in the deep white matter regions of the left anterior corona radiata (intensive treatment, 30.3 mm3 [95% CI, 16.0-44.5 mm3]; standard treatment, 80.5 mm3 [95% CI, 53.8-107.2 mm3]), left tapetum (intensive treatment, 11.8 mm3 [95% CI, 4.4-19.2 mm3]; standard treatment, 27.2 mm3 [95% CI, 19.4-35.0 mm3]), left superior fronto-occipital fasciculus (intensive treatment, 3.2 mm3 [95% CI, 0.7-5.8 mm3]; standard treatment, 9.4 mm3 [95% CI, 5.5-13.4 mm3]), left posterior corona radiata (intensive treatment, 26.0 mm3 [95% CI, 12.9-39.1 mm3]; standard treatment, 52.3 mm3 [95% CI, 34.8-69.8 mm3]), left splenium of the corpus callosum (intensive treatment, 45.4 mm3 [95% CI, 25.1-65.7 mm3]; standard treatment, 83.0 mm3 [95% CI, 58.7-107.2 mm3]), left posterior thalamic radiation (intensive treatment, 53.0 mm3 [95% CI, 29.8-76.2 mm3]; standard treatment, 106.9 mm3 [95% CI, 73.4-140.3 mm3]), and right posterior thalamic radiation (intensive treatment, 49.5 mm3 [95% CI, 24.3-74.7 mm3]; standard treatment, 102.6 mm3 [95% CI, 71.0-134.2 mm3]). This study suggests that intensive BP treatment, compared with standard treatment, was associated with a slower increase of WMLs, improved diffusion tensor imaging, and FA and CBF changes in several brain regions that represent vulnerable areas that may benefit from more strict BP control. ClinicalTrials.gov Identifier: NCT01206062.

5-Year Associations among Cerebral Arterial Pulsatility, Perivascular Space Dilation, and White Matter Lesions.

High cerebral arterial pulsatility index (PI), white matter lesions (WMLs), enlarged perivascular spaces (PVSs), and lacunar infarcts are common findings in the elderly population, and considered indicators of small vessel disease (SVD). Here, we investigate the potential temporal ordering among these variables, with emphasis on determining whether high PI is an early or delayed manifestation of SVD. In a population-based cohort, 4D flow MRI data for cerebral arterial pulsatility was collected for 159 participants at baseline (age 64-68), and for 122 participants at follow-up 5 years later. Structural MRI was used for WML and PVS segmentation, and lacune identification. Linear mixed-effects (LME) models were used to model longitudinal changes testing for pairwise associations, and latent change score (LCS) models to model multiple relationships among variables simultaneously. Longitudinal 5-year increases were found for WML, PVS, and PI. Cerebral arterial PI at baseline did not predict changes in WML or PVS volume. However, WML and PVS volume at baseline predicted 5-year increases in PI. This was shown for PI increases in relation to baseline WML and PVS volumes using LME models (R 0.24; p < 0.02 and R 0.23; p < 0.03, respectively) and LCS models ( =0.28; p=0.015 and =0.28; p=0.009, respectively). Lacunes at baseline were unrelated to PI. In healthy older adults, indicators of SVD are related in a lead-lag fashion, in which the expression of WML and PVS precedes increases in cerebral arterial PI. Hence, we propose that elevated PI is a relatively late manifestation, rather than a risk factor, for cerebral SVD. ANN NEUROL 2022;92:871-881.

In vivo stiffness of multiple sclerosis lesions is similar to that of normal-appearing white matter

In 1868, French neurologist Jean-Martin Charcot coined the term multiple sclerosis (MS) after his observation that numerous white matter (WM) glial scars felt like sclerotic tissue. Nowadays, magnetic resonance elastography (MRE) can generate images with contrast of stiffness (CS) in soft in vivo tissues and may therefore be sensitive to MS lesions, provided that sclerosis is indeed a mechanical signature of this disease.We analyzed CS in a total of 147 lesions in patients with relapsing-remitting MS, compared with control regions in contralateral brain regions, and phantom data as well as performed numerical simulations to determine the delineation limits of multifrequency MRE (20 - 40 Hz) in MS.MRE analysis of simulated waves revealed a delineation limit of approximately 10% CS for detecting 9-mm lesions (mean size in our patient population). Due to inversion bias, this limit is reached when true CS is -11% for soft and 35% for stiff lesions. In vivo MRE identified 35 stiffer lesions and 17 softer lesions compared with surrounding WM (mean stiffness: 934±82 Pa). However, a similar pattern was found in the contralateral brain, suggesting that the range of stiffness changes in WM lesions due to MS is within the normal range of WM variability and normal heterogeneity-related CS.Consequently, Charcot's original intuition that MS is a focal sclerotic disease can neither be dismissed nor confirmed by in vivo MRE. However, the observation that MS lesions do not markedly differ in stiffness from surrounding brain tissue suggests that marked tissue sclerosis is not a mechanical signature of MS. Statement of significanceMultiple sclerosis (MS) was named by J.M. Charcot after the sclerotic changes in brain tissue he found in post-mortem autopsies. Since then, nothing has been revealed about the actual stiffening of MS lesions in vivo. Studying the viscoelastic properties of plaques in their natural environment is a major challenge that can only be overcome by MR elastography (MRE). Therefore, we used multifrequency MRE to answer the question whether MS lesions in patients with a relapsing-remitting disease course are mechanically different than surrounding tissue. Our findings suggest that the range of stiffness changes in white matter lesions due to MS is within the normal range of white matter variability and in vivo tissue sclerosis might not be a mechanical signature of MS.

Progression of cortical dysfunction in CSF1R‐related leukoencephalopathy detected using single‐photon emission computed tomography

AbstractBackgroundHereditary diffuse leukoencephalopathy with spheroids (HDLS) is a rare autosomal dominant disease progressively affecting cognitive and motor functions, most often caused by mutations in the colony‐stimulating factor 1 receptor gene (CSF1R).AimTo elucidate the mechanism of disease progression, changes in white matter lesions and cortical cerebral blood flow (CBF) were evaluated in cases during various stages of the disease.MethodsAll patients were diagnosed with HDLS by confirming mutations in CSF1R. Regional CBF was evaluated using single‐photon emission computed tomography and was analyzed semiquantitatively.ResultsThree cases (2 males and 1 female, ages 51, 53, and 48 years on admission, disease duration from 1 to 8 years) were registered. All cases exhibited different CSF1R mutations and progressive frontal dysfunction. Scores of the Frontal Assessment Battery and time in the Trail Making Test worsened as the disease progressed, whereas the Mini‐Mental State Examination score remained relatively stable. MRI revealed progressive white matter lesions in the frontal lobe and atrophy of the anterior body of the corpus callosum. Regional CBF was low in the medial frontal cortex in the early case, and the area of hypoperfusion spread to the lateral frontal cortex and parietal cortex as the disease progressed. CBF was maintained in the basal ganglia, thalamus, and occipital lobes.ConclusionsHypoperfusion was initially observed in the medial frontal lobe and spread to the lateral frontal lobe and parietal lobe with disease progression. Spreading of accumulated abnormal proteins induced by mutation in CSF1R may be involved as a molecular mechanism of disease progression.

Changes of Brain Structure in Patients With Metastatic Non-Small Cell Lung Cancer After Long-Term Target Therapy With EGFR-TKI.

PurposeEpidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy is the routine treatment for patients with metastatic non-small cell lung cancer (NSCLC) harboring positive EGFR mutations. Patients who undergo such treatment have reported cognitive decline during follow-up. This study, therefore, aimed to evaluate brain structural changes in patients receiving EGFR-TKI to increase understanding of this potential symptom.MethodThe medical records of 75 patients with metastatic NSCLC (without brain metastasis or other co-morbidities) who received EGFR-TKI therapy from 2010 to 2017 were reviewed. The modified Scheltens Visual Scale and voxel-based morphometry were used to evaluate changes in white matter lesions (WML) and gray matter volume (GMV), respectively.ResultsThe WML scores were higher at the 12-month [8.65 ± 3.86; 95% confidence interval (CI), 1.60–2.35; p < 0.001] and 24-month follow-ups (10.11 ± 3.85; 95% CI, 2.98–3.87; p < 0.001) compared to baseline (6.68 ± 3.64). At the 24-month follow-up, the visual scores were also significantly higher in younger patients (3.89 ± 2.04) than in older patients (3.00 ± 1.78; p = 0.047) and higher in female patients (3.80 ± 2.04) than in male patients (2.73 ± 1.56; p = 0.023). Additionally, significant GMV loss was observed in sub-regions of the right occipital lobe (76.71 voxels; 95% CI, 40.740–112.69 voxels), left occipital lobe (93.48 voxels; 95% CI, 37.48–149.47 voxels), and left basal ganglia (37.57 voxels; 95% CI, 21.58–53.57 voxels) (all p < 0.005; cluster-level false discovery rate < 0.05).ConclusionsAn increase in WMLs and loss of GMV were observed in patients with metastatic NSCLC undergoing long-term EGFR-TKI treatment. This might reflect an unknown side-effect of EGFR-TKI treatment. Further prospective studies are necessary to confirm our findings.

Structural changes in white matter lesion patients and their correlation with cognitive impairment.

BackgroundWhite matter lesions (WMLs) play a role in cognitive decline and dementia. Little is known about gray matter (GM) changes in WMLs. This study aimed to investigate GM changes in WML patients.Materials and methodsCorrelations between altered structural volume and cognitive assessment scores were investigated. GM and white matter (WM) changes in 23 WML-vascular dementia (VaD) patients, 22 WML-non-dementia vascular cognitive impairment (VCIND) patients, and 23 healthy control (HC) subjects were examined. Gray matter density (GMD) was calculated by measuring local proportions of GM at thousands of homologous cortical locations. WM volume was obtained by fully automated software using voxel-based morphometry (VBM).ResultsWidespread GMD was significantly lower in WML patients compared to control subjects in cortical and subcortical regions (p<0.05). Greatest differences were found in the bilateral anterior cingulate cortex, inferior frontal gyrus, insula, angular gyrus, caudate, precentral gyrus, and right middle temporal gyrus, right thalamus. Secondary region of interest (ROI) analysis indicated significantly greater GMD in the bilateral caudate among WML-VCIND patients (n=22) compared to HCs (p<0.05). There was a significant difference in WM volume between WML patients and control subjects (p<0.05). Greatest differences were located in the genu/body/splenium of the corpus callosum and superior corona radiata L, and posterior corona radiata L. There was a significant association between structural changes and cognitive scores (Montreal Cognitive Assessment [MoCA] score) (p<0.05). There was no significant correlation between structural changes and Mini Mental State Examination (MMSE) scores (p>0.05).ConclusionGMD and WM volume were changed in WMLs, and the changes were detectable. Correlation between structural changes and cognitive function was promising in understanding the pathological and physiological mechanisms of WMLs.

Long-Term Magnetization Transfer Ratio Evolution in Multiple Sclerosis White Matter Lesions.

Magnetization transfer ratio (MTR), a magnetic resonance imaging technique used to assess tissue integrity, correlates with demyelination and axonal loss in multiple sclerosis (MS) lesions. In acute white matter lesions, short-term MTR changes mainly reflect demyelination and remyelination, in addition to edema and axonal and glial changes. Long-term MTR changes in MS lesions have not been studied extensively. A new quantitative image analysis method was developed to measure long-term MTR changes in MS lesions. The method was applied to a group of 59 patients and 14 healthy control subjects followed for 4 years. MTR changes in white matter lesions were analyzed, where lesion voxels were classified into six categories based on starting MTR and change over time. For each patient, the proportion of lesion voxels in each MTR-change category was calculated. Correlations between long-term MTR evolution, disability progression, and brain atrophy were investigated. The proportion of lesion voxels in the high stable category correlated with less atrophy progression, while the proportion with low and increasing MTR correlated with increased atrophy. The proportion of lesion voxels in the high and stable MTR lesion category was significantly different between MS disease subgroups. The group with disability progression had a higher proportion of lesion voxels with low and increasing MTR. These results suggest that long-term changes in MTR in white matter lesions can be used to distinguish lesion subtypes associated with MS disease progression and improve understanding of the temporal evolution of MS pathology.

Reduced perfusion in white matter lesions in multiple sclerosis

To investigate dynamic susceptibility contrast (DSC) perfusion weighted imaging (PWI) in white matter lesions (WML) in patients with multiple sclerosis (MS), using automatically generated binary masks of brain tissue. WML in MS have in some studies demonstrated perfusion abnormalities compared to normal appearing white matter (NAWM), however perfusion changes in WML in MS have in general not been well documented. DSC PWI was performed at 1.5 Tesla in 69 newly diagnosed MS patients. Parametric perfusion maps representing cerebral blood volume (CBV), cerebral blood flow (CBF) and mean transit time (MTT) were obtained. Binary masks of WML, white matter (WM) and grey matter (GM) were automatically generated and co-registered to the perfusion maps. The WML mask was manually edited and modified to correct for errors in the automatic lesion detection. Perfusion parameters were derived both from WML and NAWM using the manually modified WML mask, and using the original non-modified WML mask (with and without GM exclusion mask). Differences in perfusion measures between WML and NAWM were analyzed. CBF was significantly lower (p<0.001) and MTT significantly higher (p<0.001) in WML compared to NAWM. CBV did not show significant difference between WML and NAWM. The non-modified WML mask gave similar results as manually modified WML mask if the GM exclusion mask was used in the analysis. DSC PWI revealed lower CBF and higher MTT, consistent with reduced perfusion, in WML compared to NAWM in patients with early MS. Automatically generated binary masks are a promising tool in perfusion analysis of WML.

Differing Associations of White Matter Lesions and Lacunar Infarction with Retinal Microvascular Signs

White matter lesions (WML) and lacunar infarcts (LI) are believed to have microvascular etiologies but the exact microvascular changes occurring in each is unclear. Using the retina as a proxy, we assessed retinal microvascular changes in WML and LI. We prospectively recruited 1211 acute stroke patients. Four subgroups were identified from neuroimaging: WML alone, LI alone, both WML and LI, neither WML nor LI. Masked retinal photographs identified retinopathy and retinal arteriolar wall signs and measured retinal vascular caliber. Compared with 448 controls with neither WML nor LI, 384 patients with only WML were more likely to have retinopathy [odds ratio (OR) 1·5, 95% confidence interval (CI) 1·1 to 2·1] and enhanced arteriolar light reflex (OR 1·6, 95% CI 1·1 to 2·3); 200 patients with only LI were more likely to have arteriolar narrowing (OR 1·6, 95% CI 1·1 to 2·3) and enhanced arteriolar light reflex (OR 1·6, 95% CI 1·0 to 2·4); and 179 patients with both WML and LI were more likely to have arteriovenous nicking (OR 1·7, 95% CI 1·1 to 2·6), enhanced arteriolar light reflex (OR 2·0, 95% CI 1·3 to 3·2) and wider venules (OR 2·3, 95% CI 1·4 to 3·6). All analyses were adjusted for age, gender, study site and cardiovascular risk factors. Both WML and LI were associated with retinal microvascular signs, supporting a microvascular etiology. Differing patterns of association suggest different mechanisms may predominate, e.g. greater endothelial permeability in WML, and ischemia associated with arteriolar wall disease in LI.

White Matter Lesions Progression in Migraine with Aura: A Clinical and MRI Longitudinal Study

To prospectively evaluate longitudinal changes in white matter lesions (WMLs) in migraineurs with aura, by magnetic resonance imaging (MRI), and to correlate WMLs modifications with patients' clinical characteristics. Forty-one consecutive migraineurs with aura were followed for a mean time of 33.2 months. Patients underwent MRI at baseline and follow-up and were evaluated for cerebrovascular risk factors. Presence of WMLs on MRI was assessed by two neuroradiologists. WMLs were present in 26 subjects (63.4%) at baseline MRI. At follow-up a total of 8 patients had new WMLs (19.5%). There was a significant correlation between aura duration and number of new WMLs, and between the number of migraine attacks with aura and new WMLs. Our study demonstrates that in migraine with aura WMLs number can progress over time and suggests an association between aura features and WMLs progression. Studies with a higher number of patients are required to confirm these findings.

Longitudinal neuroimaging correlates of subjective memory impairment: 4-year prospective community study

Complaints about memory are common in older people but their relationship with underlying brain changes is controversial. To investigate the relationship between subjective memory impairment and previous or subsequent changes in white matter lesions and brain volumes. In a community cohort study of 1336 people without dementia, 4-year changes in brain magnetic resonance imaging measures were investigated as correlates of subjective memory impairment at baseline and follow-up. Subjective memory impairment at baseline was associated with subsequent change in hippocampal volume and at follow-up impairment was associated with previous change in hippocampal, cerebrospinal fluid and grey matter volume and with subcortical white matter lesion increases. All associations with volume changes were U-shaped with significant quadratic terms - associations between least decline and subjective memory impairment were potentially explained by lower baseline hippocampal volumes in the groups with least volume change. Associations between hippocampal volume change and subjective memory impairment at follow-up were independent of cognitive decline and depressive symptoms, they were stronger in participants with the apolipoprotein E (APOE) ε4 allele and in those without baseline subjective memory impairment. Complaints of poor memory by older people, particularly when new, may be a realistic subjective appraisal of recent brain changes independent of observed cognitive decline.

Serial changes in white matter lesions in a neonate with incontinentia pigmenti

We report an infant who presented with clinical manifestations of incontinentia pigmenti (IP). Despite experiencing seizures in the early neonatal period, the patient had normal growth and development until recently. However, follow-up magnetic resonance imaging revealed sequential changes in white matter lesions. The pathogenesis of neurological involvement in IP has not been clearly elucidated and appears to be associated with various mechanisms, including developmental, destructive, and vascular processes. We have attempted to explain the pathogenesis of IP through these changes.

Physical activity and white matter lesion progression

We evaluated the association between physical activity and changes in white matter lesions (WMLs) on MRI in a sample of 179 older adults comprising 59 incident cases of Alzheimer disease, 60 persons with mild cognitive impairment, and 60 persons who remained cognitively stable over a median 5-year follow-up. Physical activity was not significantly associated with a decreased rate of periventricular or deep WML progression.

Magnetization transfer measurements of cerebral white matter in patients with myotonic dystrophy

To determine whether patients with myotonic dystrophy (MyD) have structural changes in the cerebral white matter, we performed magnetization transfer (MT) imaging of the cerebral white matter in 14 MyD patients and 11 age-matched normal controls. We calculated MT ratios in both the white matter lesions (WMLs) and the normal-appearing white matter (NAWM) of MyD patients using region of interest (ROI) analysis. MT ratios in WMLs were markedly decreased, and all ROIs in NAWM also showed significantly lower MT ratios in MyD patients than in normal controls. The average MT ratio of all ROIs in WMLs and NAWM in each patient showed a significant negative correlation with duration of illness, but not with the patient's age or age at onset. The results of the present study indicate not only the presence of pathological changes in WMLs but also the widespread involvement of NAWM in MyD patients. The results also suggest that structural changes in the white matter may be progressive during the clinical course of MyD.

Vascular changes in white matter lesions of Alzheimer's disease.

The pathogenesis of white matter lesions observed in Alzheimer's disease (AD) is not completely clear. We tested the hypothesis that white matter lesions are correlated with medullary artery sclerosis rather than with amyloid angiopathy. A total of 57 brains were examined, including 39 derived from patients with AD and 13 from patients with Binswanger's disease (BD) along with 5 from non-neurological patients. Moderate or severe amyloid deposits in the meningocortical segment were observed in 32 out of 39 AD patients (82.1%), and in 2 out of 13 BD patients (15.4%). These deposits were not observed in the white matter segment, except for 2 patients with AD. The BD patients invariably had marked white matter lesions and fibrohyalinosis in the medullary arteries, with a mean sclerotic ratio of 48.1%. In contrast, the AD patients had mild or moderate white matter lesions and a sclerotic ratio of 37.9%, which was significantly greater than the controls. The scores for white matter lesions were correlated with the sclerotic ratio of the medullary arteries, but not with the ages of onset or the scores for amyloid angiopathy. Although amyloid angiopathy is an independent risk of white matter lesions, its role is limited in the pathogenesis of those associated with AD. Wall thickening of the medullary arteries, likely due to fibrohyalinosis, is closely correlated with the white matter lesions in AD, thus indicating a heterogeneity in its etiology.