Total Lesion Volume Research Articles

RADI-10. THERAPEUTIC EFFECTS OF fSRS IN 44 CASES OF BRAIN METASTASES OF NSCLC WITH A MAXIMUM DIAMETER ≥ 4CM AND ANALYSIS OF ITS PROGNOSTIC FACTORS

OBJECTIVE: To analyze the therapeutic effects of fSRS on brain metastases of NSCLC with a maximum diameter ≥ 4 cm, and explore the prognostic factors. METHODS: A retrospective analysis was conducted on the clinical data of 44 cases of brain metastases of NSCLC with a maximum diameter ≥ 4 cm in Guangdong Sanjiu Brain Hospital from January 2006 to December 2016. RANO criteria were adopted for imaging evaluation at 3 months after completion of radiotherapy. One- and 2-year survival rates were calculated and the differences in survival rates between groups were analyzed with Log-rank test. Kaplan-Meier method was used in univariate analysis to investigate the effects of KPS, RPA classification, number of metastases, total lesion volume, systemic treatment and surgery on prognosis; and Cox regression model in multivariate analysis. RESULTS: The postoperative imaging evaluation showed that there were 5 cases of CR, 20 of PR, 12 of SD and 7 of PD. The median PFS, OS, 1- and 2-year survival rates were 6 months, 16 months, 65.9% and 20.5%, respectively. KPS, RPA classification, number of metastases and surgery had no significant correlations with prognosis. However, systemic treatment and the maximum lesion volume ＜28.3cc were considered as favorable factors related to prognosis (P=0.046, 0.027). Moreover, the maximum lesion volume ＜28.3cc was found to be the independent prognostic factor for the survival (P=0.035). CONCLUSION: Treatment of brain metastases of NSCLC with a maximal diameter ≥4 cm with fSRS is proved to be feasible. The maximum lesion volume is related to prognosis. Systemic treatment (chemotherapy, TKI treatment, etc.) may improve prognosis, but more cases are needed to investigate the prognostic significance.

In Organ-confined Prostate Cancer, Tumor Quantitation Not Found to Aid in Prediction of Biochemical Recurrence.

In the eighth edition AJCC staging, all organ-confined disease is assigned pathologic stage T2, without subclassification. We investigated whether total tumor volume (TTV) and/or maximum tumor diameter (MTD) of the index lesion are useful in improving prediction of biochemical recurrence (BCR) in pT2 patients. We identified 1657 patients with digital tumor maps and quantification of TTV/MTD who had pT2 disease on radical prostatectomy (RP). Multivariable Cox regression models were used to assess whether TTV and/or MTD are independent predictors of BCR when adjusting for a base model incorporating age, preoperative prostate-specific antigen, RP grade group, and surgical margin status. If either tumor quantification added significantly, we calculated and reported the c-index. Ninety-five patients experienced BCR after RP; median follow-up for patients without BCR was 5.7 years. The c-index was 0.737 for the base model. Although there was some evidence of an association between TTV and BCR (P=0.088), this did not meet conventional levels of statistical significance and only provided a limited increase in discrimination (0.743; c-index improvement: 0.006). MTD was not associated with BCR (P>0.9). In analyses excluding patients with grade group 1 on biopsy who would be less likely to undergo RP in contemporary practice (622 patients; 59 with BCR), TTV/MTD was not a statistically significant predictor (P=0.4 and 0.8, respectively). Without evidence that tumor quantitation, in the form of either TTV or MTD of the index lesion, is useful for the prediction of BCR in pT2 prostate cancer, we cannot recommend its routine reporting.

ГЕМОЦИТИ ІНТАКТНОЇ ТА ІНВАЗОВАНОЇ ТРЕМАТОДАМИ ЖАБУРНИЦІ КИТАЙСЬКОЇ (MOLLUSCA, UNIONIDAE, ANODONTINAE)

The hemolymph of Sinanodonta woodiana (Lea, 1834) consists of plasma and cells of four types: prohemocytes (cambial cells), macronucleocytes, basophilic and eosinophilic granulocytes. The three latter cell types derive from the cambial cells though mitosis. The cellular sizes are: prohemocytes 14.3±0.4, basophilic granulocytes 20.9±0.7, young eosinophilic granulocytes 23.8±0.6, older eosinophilic granulocytes 25.7±0.1, macronucleocytes 26.1±0.3. All cells and their nuclei are roundish. Nuclear chromatin is either fine-grained fairly evenly distributed in the karyoplasm (in basophilic granulocytes), or more or less grouped dark-colored small (2-5-6) chromatin blocks. NC-ratio is maximum in macronucleocytes (0.6±0.01). NC-ratio of prohemocytes is 0.4±0.01, that of basophilic granulocytes is 0.3±0.01. NC-ratio of eosinophilic granulocytes is 0.2±0.01. Eosinophilic cells prevail in hemolymph elements: the young eosinophilic granulocytes make up 25.1±0.4 % and the older eosinophilic cells are up to 27.9±0.6 % of all hemocytes. The major functions of hemolymph cells are transport and protection.Transport is particularly pronounced in basophilic granulocytes in the form of phagocytosis. The protective function of hemocytes of different categories is manifested in a different way. Thus, some of the basophilic granulocytes develop into nephrocytes, which accumulate numerous (11-23) vacuoles of yellow-green-brown color. The vacuoles are subsequently excreted by the mollusk through the kidneys. The protective function of eosinophilic granulocytes is realized as false agglutination (these hemocytes clog into lumps that close wounds), which helps preventing blood loss. Also, eosinophilic granulocytes merge into multinucleated plasmodium, accumulating in large quantities around various foreign bodies (parasites or fragments of destroyed tissues) and encapsulating them to isolate from host tissues. At Northern Black Sea Coast, Chinese pond mussel is a common intermediate host of the trematode Rhipidocotyle companula Dujardin, 1845.The trematode inhabits the mollusk’s gonads. The parasitic sporocysts and cercariae were found in 29 % of examined mollusk specimens. Infestations were weak (up to 10 % of gonads were affected) in 22.4 % of infected mollusks, moderate (10 to 50 % of gonads) in 70 % of contaminated mollusks. Only 7.6 % of infected pond mussels were hyperinfected (100 % of gonads were affected).Weak trematode infestation is accompanied by localized damage. The total number and volume of parasitic focal lesions are generally insignificant. Moderate infection, and especially a hyperinfection cause not only the lesions in the hostal biotope, but also the overall pathological process in mollusk hosts. Simultaneously, the prohemocytes and basophilic granulocytes as well as their nuclei reduce in size. The total number of prohemocytes also declines by 1.7 times. The greatest decrease in the nuclear-cytoplasmic ratio (by a factor of 1.5-2) is noted also for prohemocytes and basophilic granulocytes. The vacuolization of karyoplasm and cytoplasm, the basophilization of cytoplasm, the degenerative changes in hemocyte nuclei (karyopicnosis, karyorexis, karyolysis), and the total number of aging and dying hemocytes are directly related to the level of infection intensity.

Relapse numbers and earlier intervention by disease modifying drugs are related with progression of less brain atrophy in patients with multiple sclerosis

Long term effect between disease-modifying drugs (DMDs) treatment duration and brain atrophy rate has not been fully investigated in patients with relapsing-remitting MS (RRMS). The aim of this study was to investigate whether DMDs could slow down the progression of brain atrophy in patients with RRMS by comparing DMDs-treated group with non-treated group during a certain period of time.This was a retrospective investigation. Forty-nine RRMS patients underwent two brain MRI scans more than one year apart. Between scans, patients were treated with fingolimod (n = 16), interferon-beta (n = 23) or not treated with DMD (n = 10). Correlations between clinical characteristics and brain volume were calculated by statistical parametric mapping-12.In all 49 patients, the total attack number before 1st MRI scan and the annualized rate of total lesion volume change between the two scans showed a positive correlation with annualized atrophy rate of grey matter volume (GMV) plus white matter volume (WMV). In patients with DMDs (n = 39), the period from drug initiation to 1st MRI scan was negatively correlated with the annualized atrophy rate of GMV + WMV and number of attacks between scans.The number of total previous attacks could be a predictor of subsequent MS progression. Early intervention by DMDs could prevent brain atrophy in patients with MS.

The relationship between ischaemic brain lesions and cognitive outcome after aneurysmal subarachnoid haemorrhage

BackgroundCerebral ischaemia is thought to be an important determinant of cognitive outcome after aneurysmal subarachnoid haemorrhage (aSAH), but the exact relationship is unclear. We studied the effect of ischaemic brain lesions during clinical course on cognitive outcome 2 months after aSAH.MethodsWe studied 74 consecutive patients admitted to the University Medical Center Utrecht who had MRI post-coiling (3–21 days post-aSAH) and neuropsychological examination at 2 months. An ischaemic lesion was defined as hyperintensity on T2-FLAIR and DWI images. We measured both cognitive complaints (subjective) and cognitive functioning (objective). The relationship between ischaemic brain lesions and cognitive outcome was analysed by logistic regression analyses.ResultsIn 40 of 74 patients (54%), 152 ischaemic lesions were found. The median number of lesions per patient was 2 (1–37) and the median total lesion volume was 0.2 (0–17.4) mL. No difference was found between the group with and the group without ischaemic lesions with respect to the frequency of cognitive complaints. In the group with ischaemic lesions, significantly more patients (55%) showed poor cognitive functioning compared to the group without ischaemic lesions (26%) (OR 3.4, 95% CI 1.3–9.1). We found no relationship between the number and volume of the ischaemic lesions and cognitive functioning.ConclusionsIschaemic brain lesions detected on MRI during clinical course after aSAH is a marker for poor cognitive functioning 2 months after aSAH, irrespective of the number or volume of the ischaemic lesions. Network or connectivity studies are needed to better understand the relationship between location of the ischaemic brain lesions and cognitive functioning.

Automated Detection and Segmentation of Multiple Sclerosis Lesions Using Ultra-High-Field MP2RAGE.

The aim of this study was to develop a new automated segmentation method of white matter (WM) and cortical multiple sclerosis (MS) lesions visible on magnetization-prepared 2 inversion-contrast rapid gradient echo (MP2RAGE) images acquired at 7 T MRI. The proposed prototype (MSLAST [Multiple Sclerosis Lesion Analysis at Seven Tesla]) takes as input a single image contrast derived from the 7T MP2RAGE prototype sequence and is based on partial volume estimation and topological constraints. First, MSLAST performs a skull-strip of MP2RAGE images and computes tissue concentration maps for WM, gray matter (GM), and cerebrospinal fluid (CSF) using a partial volume model of tissues within each voxel. Second, MSLAST performs (1) connected-component analysis to GM and CSF concentration maps to classify small isolated components as MS lesions; (2) hole-filling in the WM concentration map to classify areas with low WM concentration surrounded by WM (ie, MS lesions); and (3) outlier rejection to the WM mask to improve the classification of small WM lesions. Third, MSLAST unifies the 3 maps obtained from 1, 2, and 3 processing steps to generate a global lesion mask. Quantitative and qualitative assessments were performed using MSLAST in 25 MS patients from 2 research centers. Overall, MSLAST detected a median of 71% of MS lesions, specifically 74% of WM and 58% of cortical lesions, when a minimum lesion size of 6 μL was considered. The median false-positive rate was 40%. When a 15 μL minimal lesions size was applied, which is the approximation of the minimal size recommended for 1.5/3 T images, the median detection rate was 80% for WM and 63% for cortical lesions, respectively, and the median false-positive rate was 33%. We observed high correlation between MSLAST and manual segmentations (Spearman rank correlation coefficient, ρ = 0.91), although MSLAST underestimated the total lesion volume (average difference of 1.1 mL), especially in patients with high lesion loads. MSLAST also showed good scan-rescan repeatability within the same session with an average absolute volume difference and F1 score of 0.38 ± 0.32 mL and 84%, respectively. We propose a new methodology to facilitate the segmentation of WM and cortical MS lesions at 7 T MRI, our approach uses a single MP2RAGE scan and may be of special interest to clinicians and researchers.

Ischemic lesion growth in acute stroke: Water uptake quantification distinguishes between edema and tissue infarct

Infarct growth from the early ischemic core to the total infarct lesion volume (LV) is often used as an outcome variable of treatment effects, but can be overestimated due to vasogenic edema. The purpose of this study was (1) to assess two components of early lesion growth by distinguishing between water uptake and true net infarct growth and (2) to investigate potential treatment effects on edema-corrected net lesion growth. Sixty-two M1-MCA-stroke patients with acute multimodal and follow-up CT (FCT) were included. Ischemic lesion growth was calculated by subtracting the initial CTP-derived ischemic core volume from the LV in the FCT. To determine edema-corrected net lesion growth, net water uptake of the ischemic lesion on FCT was quantified and subtracted from the volume of uncorrected lesion growth. The mean lesion growth without edema correction was 20.4 mL (95% CI: 8.2–32.5 mL). The mean net lesion growth after edema correction was 7.3 mL (95% CI: −2.1–16.7 mL; p < 0.0001). Lesion growth was significantly overestimated due to ischemic edema when determined in early-FCT imaging. In 18 patients, LV was lower than the initial ischemic core volume by CTP. These apparently “reversible” core lesions were more likely in patients with shorter times from symptom onset to imaging and higher recanalization rates.

Longitudinal Characterization of Cortical Lesion Development and Evolution in Multiple Sclerosis with 7.0-T MRI.

Background Cortical lesions develop early in multiple sclerosis (MS) and play a major role in disease progression. MRI at 7.0 T shows high sensitivity for detection of cortical lesions as well as better spatial resolution and signal-to-noise ratio compared with lower field strengths. Purpose To longitudinally characterize (a) the development and evolution of cortical lesions in multiple sclerosis across the cortical width, sulci, and gyri; (b) their relation with white matter lesion accrual; and (c) the contribution of 7.0-T cortical and white matter lesion load and cortical thickness to neurologic disability. Materials and Methods Twenty participants with relapsing-remitting MS and 13 with secondary progressive MS, along with 10 age-matched healthy controls, were prospectively recruited from 2010 to 2016 to acquire, in two imaging sessions (mean interval, 1.5 years), 7.0-T MRI T2*-weighted gradient-echo images (0.33 × 0.33 × 1.0 mm3) for cortical and white matter lesion segmentation and 3.0-T T1-weighted images for cortical surface reconstruction and cortical thickness estimation. Cortical lesions were sampled through the cortex to quantify cortical lesion distribution. The Expanded Disability Status Scale (EDSS) was used to assess neurologic disability. Nonparametric statistics assessed differences between and within groups in MRI metrics of cortical and white matter lesion burden; regression analysis explored associations of disability with MRI metrics. Results Twenty-five of 31 (81%) participants developed new cortical lesions per year (intracortical, 1.3 ± 1.7 vs leukocortical, 0.7 ± 1.9; P = .04), surpassing white matter lesion accrual (cortical, 2.0 ± 2.8 vs white matter, 0.7 ± 0.6; P = .01). In contrast to white matter lesions, cortical lesion accrual was greater in participants with secondary progressive MS than with relapsing-remitting MS (3.6 lesions/year ± 4.2 vs 1.1 lesions/year ± 0.9, respectively; P = .03) and preferentially localized in sulci. Total cortical lesion volume independently predicted baseline EDSS (β = 1.5, P < .001) and EDSS changes at follow-up (β = 0.5, P = .003). Conclusion Cortical lesions predominantly develop intracortically and within sulci, suggesting an inflammatory cerebrospinal fluid-mediated lesion pathogenesis. Cortical lesion accumulation was prominent at 7.0 T and independently predicted neurologic disability progression. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Filippi and Rocca in this issue.

Characterization of gray-matter multiple sclerosis lesions using double inversion recovery, diffusion, contrast-enhanced, and volumetric MRI

PurposeTo investigate gray-matter (GM) lesions in relapsing-remitting multiple sclerosis (MS) using double-inversion recovery (DIR) MRI, determine GM lesions prevalence, spatial distribution and characterize their contrast-enhancement, diffusion characteristics and compare them to white-matter (WM) lesions. This is the first study, to our knowledge, to investigate GM MS lesions using double-inversion recovery MRI, to determine GM lesion prevalence and location, and characterize contrast-enhancement and diffusion characteristics, compared to WM lesion characteristics in the same patients. We also correlated GM lesion counts, volume and apparent diffusion coefficient (ADC) with total brain, WM, and GM volumes, as well as 25-foot walk test as a clinical disability. Materials and MethodsThis retrospective study included 44 relapsing-remitting MS patients (12M/32F, 41 ± 13 years) and 24 age-matched healthy controls (14M/10F, 36 ± 13 years). Lesions were segmented based on DIR and grouped into GM, subcortical WM, and periventricular WM lesions. ADC was tabulated for contrast-enhancing and non-enhancing lesions. Unpaired two sample t-tests were used for comparison between groups. Linear regression was used to evaluate the relationship between number of GM lesions, number of total lesions, total GM lesion volume, and total WM lesion volume with brain volumes and clinical data. ResultsGM MS lesions were present in the majority (86.4%, 38/44) of RRMS patients based on DIR, suggesting GM damage plays an important role in MS pathogenesis. The majority of the GM lesions were located in the frontal lobe. The percentage of lesions in GM that were contrast-enhanced was similar to those in WM, suggesting that blood-brain barrier integrity is likely affected similarly in GM and WM. Contrast-enhanced GM lesions showed higher ADC. GM lesion count and volume were correlated with global and regional brain atrophy, and with more severe disability group. ConclusionThis study characterized GM MS lesions using double-inversion recovery, contrast-enhanced and diffusion MRI. Understanding GM lesion pathophysiology using MRI in vivo, may prove useful for improving targeted therapy and monitoring disease progression.

Brain regional volume estimations with NeuroQuant and FIRST: a study in patients with a clinically isolated syndrome.

Brain volume estimates from magnetic resonance images (MRIs) are of great interest in multiple sclerosis, and several automated tools have been developed for this purpose. The goal of this study was to assess the agreement between two tools, NeuroQuant® (NQ) and FMRIB's Integrated Registration Segmentation Tool (FIRST), for estimating overall and regional brain volume in a cohort of patients with a clinically isolated syndrome (CIS). In addition, white matter lesion volume was estimated with NQ and the Lesion Segmentation Toolbox (LST). One hundred fifteen CIS patients were analysed. Structural images were acquired on a 3.0-T system. The volume agreement between methods (by estimation of the intraclass correlation coefficient) was calculated for the right and left thalamus, caudate, putamen, pallidum, hippocampus, and amygdala, as well as for the total intracranial volume and white matter lesion volume. In general, the estimated volumes were larger by NQ than FIRST, except for the pallidum. Agreement was low (ICC < 0.40) for the smaller structures (amygdala and pallidum) and fair to good (ICC > 0.40) for the remaining ones. Agreement was fair for lesion volume (ICC = 0.61), with NQ estimates lower than LST. Agreement between NQ and FIRST brain volume estimates depends on the size of the structure of interest, with larger volumes achieving better agreement. In addition, concordance between the two tools does seem to be dependent on the presence of brain lesions.

03:45 PM Abstract No. 301 Percutaneous cryoablation for the treatment of extra-abdominal desmoid tumors

Desmoid tumors are a rare form of locally invasive, benign neoplasms that develop along aponeurotic structures with high recurrence rate after surgical resection. The purpose of this study was to evaluate the safety and efficacy of cryoablation for local disease control. A retrospective search of our single-institution database identified 23 patients with extra-abdominal desmoid tumors who were treated with percutaneous cryoablation as both de novo (61% pts) and salvage (39% pts) treatment in 28 sessions between 2014 and 2018. Mean lesion diameter was 7.0 cm, ranging from 1.1 - 14.0 cm. 48% of patients were treated with the goal of complete ablation, while 52% were treated for palliative debulking. Patient age ranged from 16 to 77 years. Tumors were treated in the abdominal wall, chest wall, shoulder girdle, upper extremity, hip girdle, lower extremity, and head and neck. Imaging was evaluated for baseline tumor size, MR characteristics, and enhancing tumor volume. Technical success was achieved in 100% of patients. 90% of patients who were symptomatic on presentation showed clinical improvement following ablation. One patient suffered a major procedural complication consisting of significant neuropraxia. The average imaging follow-up was 14.6 months (SD ± 10.9). Of 11 patients with follow-up imaging at 12 months, the enhancing tumor volume showed either complete response (CR) or partial response (PR) in all patients (CR 27%, PR 73%), and the total lesion volume showed either CR or PR in 9 of 11 patients. No treatments demonstrated rapid post-ablation growth or track seeding. Three patients underwent repeat cryoablation for either residual or progressive disease. Cryoablation for desmoid tumors demonstrates a high degree of symptom improvement and local tumor control on early follow-up imaging with relatively few side effects. Study limitations include variable follow-up, small sample size, and the retrospective nature of this case series; however, further studies should be pursued as these data provide promising results.

A novel multi-atlas and multi-channel (MAMC) approach for multiple sclerosis lesion segmentation in brain MRI

This paper presents a novel approach for automatic segmentation of MS lesion including both of number and volume. The novelty includes the combination of the multiplicative intrinsic component optimization algorithm (Li et al. in Magn Reson Imaging 32:913–923, 2014) in bias field correction and normal tissue segmentation simultaneously, and the development of a multi-atlas and multi-channel (MAMC) segmentation approach. The first research focus is the classification of brain tissue into white matter, cerebrospinal fluid and gray matter in T1-w image and FLAIR image. The second research focus is the segmentation of MS lesion in white matter region using atlas. In label fusion, the coefficient as a specific weight is assigned to target label image based on the correlation function between atlases. This novel MAMC approach is evaluated by 20 training cases obtained from Medical Image Computing and Computer Aided Intervention Society 2008 MS Lesions Segmentation Challenge. The numerical results are presented in terms of accuracy, specificity and absolute volume difference. A comparison of MAMC approach and other conventional approaches is presented in terms of the true positive rate and the positive predictive value. Furthermore, the total lesion volume is calculated and compared with expert delineation. It can be seen that the MAMC approach is able to acquire a larger mean value of the Dice similarity coefficient than the other conventional approaches do. Therefore, this novel approach is an added value for the clinical evaluation of MS patients.

Abstract TP323: Novel Combinatory Therapy With LAU-0901 Plus NPD1 for Experimental Ischemic Stroke

Objective: Acute ischemic stroke triggers complex neurovascular, neuroinflammatory, and synaptic alterations. Our study tested the prediction that blocking platelet-activating factor-receptors (PAF-Rs)-induced pro-inflammatory signaling plus administering a docosanoid after middle cerebral artery occlusion (MCAo) would lead to sustained neurological recovery. Thus we used two small molecules: a) LAU-0901, an antagonist of the PAF-R that blocks pro-inflammatory signaling and that has shown promising efficacy in a stroke model; and b) a bioactive derivative of docosahexaenoic acid (DHA), the docosanoid Neuroprotectin D1 (NPD1), which activates cell-survival pathways and possesses potent anti-inflammatory and neuroprotective activity in the brain. Methods: Sprague-Dawley rats were anesthetized with isoflurane/nitrous oxide and received 2h MCAo by intraluminal suture. Neurological status was evaluated on days 1, 3 and 7; a grading scale of 0-12 was employed. Animals were treated with LAU-0901 (i.p. 30mg/kg, 2h after onset of stroke), NPD1 (i.v. 333mg/kg, 3h after onset of stroke) and vehicles (cyclodextrin and saline). There were four groups: LAU-0901+ NPD1; LAU-0901+saline; Cyclodextrin+ NPD1; and cyclodextrin+saline. On day 7, ex vivo MRI of the brains was conducted using 11.7 T MRI. Results: LAU-0901 and NPD1 treatments alone improved behavioral scores compared to vehicle groups by 16-44%. The neuroprotective effect was enhanced using the LAU-0901+NPD1, which resulted in improved behavioral scores up to 54% on day 7. Total lesion volumes, which were computed using T2WI, were significantly reduced by 62% with LAU-0901+NPD1 treatment compared to vehicle-treated groups. Conclusion: We are currently exploring the detailed molecular mechanisms involved in the combination treatment of the PAF-R antagonist, LAU-0901, plus NPD1. The synergistic neuroprotection observed here for the post-ischemic brain provide the basis to explore therapeutic translational avenues for ischemic stroke.

Influence of hemispheric white matter lesions and migraine characteristics on cortical thickness and volume

Background/AimMigraine-related intracerebral white matter lesions (WMLs) are likely to be microvascular in nature and can be found in all hemispheric lobes. The aim of this study was to investigate migraine patients with or without WMLs to see the effects of these tissue damages on cortical thickness and volume. The role of migraine characteristics (duration of headache, attack frequency, estimated lifetime attack number, aura) was also tested.MethodsAs study participants, 161 female migraine patients (63 with aura; 52 with WMLs) and 40 age-matched healthy female subjects were enrolled in the study. None of the included migraine patients’ headache or aura (where present) was unilaterally side-locked. Patients and controls were all right handed. Except for migraine, patients were free of any medical comorbidity. Cortical reconstruction and segmentation were performed on the 3D T1-weighted images using Freesurfer 5.3 image analysis suite. The automatic cortical parcellation was based on Freesurfer’s Desikan–Killiany–Tourville atlas, which has 31 cortical regions per hemisphere. The segmented regions were divided into five lobes (frontal, parietal, temporal, occipital, insula). Since the left and right differences in lobar and insular volumes/thicknesses were not different among our groups, volume and cortical thickness were calculated for corresponding bilateral lobes.ResultsThere was no significant difference in age between the whole migraine and the control groups. Migraineurs with WMLs (L+ patients) were significantly older than lesion-free (L-) patients (P = 0.0003) and controls (P = 0.018). Disease duration (P = 0.003), the total number of migraine attacks (P = 0.022) and the rate of aura (P = 0.0003) were significantly higher in L+ patients than in L- patients. Cortical thickness and volume measurements of lobes were not statistically different between the three groups (L+, L-, control). Age showed a significant negative association with both thickness and volume in each examined lobe (P < 0.001). Intracranial volume (ICV) showed a significant positive association with all regional volumes (P < 0.001). There were no significant group*age, group*ICV, or age*ICV interactions. None of the migraine characteristics were selected by stepwise linear regression as significant predictors of cortical thickness or volume. Only age (for both thickness and volume) and ICV (for volume) were identified as significant predictors (P < 0.001). When the L + group was divided into two subgroups by median split of total and lobar lesion number and volume, the cortical measures did not show any significant difference between the groups with low vs. high lesion number/volume by stepwise linear regression.ConclusionsIn a female migraine group, we found that the WMLs and clinical migraine characteristics have no effect on cortical thickness and volume of bilateral lobes. Lobar cortical thicknesses were equivalent within the range of ±0.1 mm. Only age and ICV proved to be significant predictors; the former for both cortical thickness and volume, while the latter for cortical volume.

Relevance of brain lesion location for cognition in vascular mild cognitive impairment.

BackgroundVascular mild cognitive impairment (VMCI) is a potentially transitional state between normal aging and vascular dementia. The presence of macroscopic white matter lesions (WML) of moderate or severe extension on brain MRI is the hallmark of the VMCI.ObjectiveTo assess the clinical relevance of the frequency of WML in patients with VMCI independently of total lesion volume (LV).MethodsIn this multicenter study, we included 110 patients with VMCI (age: 74.3 ± 6.6 years; sex: 60 women). Cognitive assessment was performed with the VMCI-Tuscany Neuropsychological Battery, which allowed to identify four VMCI groups: amnestic single (n = 9) and multi-domain (n = 76), non-amnestic single- (n = 10) and multi-domain (n = 15). Distribution and frequency of WML on MRI FLAIR images were evaluated with lesion probability map (LPM). Voxelwise statistics was performed with nonparametric permutation tests, controlling for age, sex, slice thickness, center, magnetic field strength, total LV and head size (p < .01, family-wise error-corrected for multiple comparisons across space).ResultsLPM of the WML had a fairly symmetric and widespread distribution across brain. A higher frequency of WML along association tracts of the WM such as inferior longitudinal fascicle, inferior fronto-occipital fascicle and superior longitudinal fascicle, was correlated with worst cognitive scores at the Trail Making Test Part A and Copy of the Rey–Osterrieth Complex Figure. The non-amnestic groups showed a higher frequency of WML in the anterior cingulum and superior longitudinal fascicle close to the frontal gyrus.ConclusionsOur study showed that in patients with VMCI, independently of total LV, the higher frequency of lesions along association tracts of the WM, which mediate intrahemispheric long-range connectivity, is related with psychomotor speed and constructional praxis. Moreover, a prevalence of lesions in the frontal WM seems to characterize VMCI patients with involvement of non-amnestic domains.

Cross-sectional and longitudinal associations between total and regional white matter hyperintensity volume and cognitive and motor function in Parkinson's disease.

BackgroundWhite matter hyperintensities (WMH) are frequently observed on T2-weighted brain magnetic resonance imaging studies of healthy older adults and have been linked with impairments in balance, gait, and cognition. Nonetheless, few studies have investigated the longitudinal effects of comorbid WMH on cognition and motor function in Parkinson's disease.MethodsThe Lesion Segmentation Tool for Statistical Parametric Mapping was used to obtain total lesion volume and map regional WMH probabilities in 29 PD and 42 control participants at two study visits 18 months apart. Both cross-sectional and longitudinal comparisons were made between composite scores in the domains of executive function, memory, and language, and Unified Parkinson's Disease Rating Scale (UPDRS) scores.ResultsWe found no difference between disease and control groups in total WMH volume or progression during the study. Greater regional and global WMH at baseline was more strongly associated with lower executive function in PD subjects than in controls. Increased regional WMH was also more strongly associated with impaired memory performance in PD relative to controls. Longitudinally, no associations between cognitive change and total or regional WMH progression were detected in either group. A positive relationship between baseline regional WMH and total UPDRS scores was present in the control group, but not PD. However, greater WMH increase was associated with a greater increase in UPDRS motor sub-scores in PD.ConclusionsThese findings suggest that although PD patients do not experience greater mean WMH load than normal aged adults, comorbid WMH do exacerbate cognitive and motor symptoms in PD.

Value of fluid-attenuated inversion recovery MRI data analyzed by the lesion segmentation toolbox in amyotrophic lateral sclerosis.

BackgroundMRI fluid‐attenuated inversion recovery (FLAIR) studies reported hyperintensity in the corticospinal tract and corpus callosum of patients with amyotrophic lateral sclerosis (ALS).PurposeTo evaluate the lesion segmentation toolbox (LST) for the objective quantification of FLAIR lesions in ALS patients.Study TypeRetrospective.PopulationTwenty‐eight ALS patients (eight females, mean age: 50 range: 24–73, mean ALSFRS‐R sum score: 36) were compared with 31 age‐matched healthy controls (12 females, mean age: 45, range: 25–67). ALS patients were treated with riluzole and additional G‐CSF (granulocyte‐colony stimulating factor) on a named patient basis.Field Strength/Sequence1.5 T, FLAIR, T1‐weighted MRI.AssessmentThe lesion prediction algorithm (LPA) of the LST enabled the extraction of individual binary lesion maps, total lesion volume (TLV), and number (TLN). Location and overlap of FLAIR lesions across patients were investigated by registration to FLAIR average space and an atlas. ALS‐specific functional rating scale revised (ALSFRS‐R), disease progression, and survival since diagnosis served as clinical correlates.Statistical TestsUnivariate analysis of variance (ANOVA), repeated‐measures ANOVA, t‐test, Bravais‐Pearson correlation, Chi‐square test of independence, Kaplan–Meier analysis, Cox‐regression analysis.ResultsBoth ALS patients and healthy controls exhibited FLAIR alterations. TLN significantly depended on age (F(1,54) = 24.659, P < 0.001) and sex (F(1,54) = 5.720, P = 0.020). ALS patients showed higher TLN than healthy controls depending on sex (F(1, 54) = 5.076, P = 0.028). FLAIR lesions were small and most pronounced in male ALS patients. FLAIR alterations were predominantly detected in the superior and posterior corona radiata, anterior capsula interna, and posterior thalamic radiation. Patients with pyramidal tract (PT) lesions exhibited significantly inferior survival than patients without PT lesions (P = 0.013). Covariate age exhibited strong prognostic value for survival (P = 0.015).Data ConclusionLST enables the objective quantification of FLAIR alterations and is a potential prognostic biomarker for ALS. Level of Evidence: 3 Technical Efficacy: Stage 2J. Magn. Reson. Imaging 2019;50:552–559.

Geostatistical Analysis of White Matter Lesions in Multiple Sclerosis Identifies Gender Differences in Lesion Evolution.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system with presumed autoimmune origin. The development of lesions within the gray matter and white matter, which are highly variable with respect to number, total volume, morphology and spatial evolution and which only show a limited correlation with clinical disability, is a hallmark of the disease. Population-based studies indicate a distinct outcome depending on gender. Here, we studied gender-related differences in the evolution of white matter MS-lesions (MS-WML) in early MS by using geostatistical methods. Within a 3 years observation period, a female and a male MS patient group received disease modifying drugs and underwent standardized annual brain magnetic resonance imaging, accompanied by neurological examination. MS-WML were automatically extracted and the derived binary lesion masks were subject to geostatistical analysis, yielding quantitative spatial-statistics metrics on MS-WML pattern morphology and total lesion volume (TLV). Through the MS-lesion pattern discrimination plot, the following differences were disclosed: corresponding to gender and MS-WML pattern morphology at baseline, two female subgroups (F1, F2) and two male subgroups (M1, M2) are discerned that follow a distinct MS-WML pattern evolution in space and time. F1 and M1 start with medium-level MS-WML pattern smoothness and TLV, both behave longitudinally quasi-static. By contrast, F2 and M2 start with high-level MS-WML pattern smoothness and medium-level TLV. F2 and M2 longitudinal development is characterized by strongly diminishing MS-WML pattern smoothness and TLV, i.e., continued shrinking and break-up of MS-WML. As compared to the male subgroup M2, the female subgroup F2 shows continued, increased MS-WML pattern smoothness and TLV. Data from neurological examination suggest a correlation of MS-WML pattern morphology metrics and EDSS. Our results justify detailed studies on gender-related differences.

Structural MRI correlates of PASAT performance in multiple sclerosis

BackgroundThe Paced Auditory Serial Addition Test (PASAT) is a useful cognitive test in patients with multiple sclerosis (MS), assessing sustained attention and information processing speed. However, the neural underpinnings of performance in the test are controversial. We aimed to study the neural basis of PASAT performance by using structural magnetic resonance imaging (MRI) in a series of 242 patients with MS.MethodsPASAT (3-s) was administered together with a comprehensive neuropsychological battery. Global brain volumes and total T2-weighted lesion volumes were estimated. Voxel-based morphometry and lesion symptom mapping analyses were performed.ResultsMean PASAT score was 42.98 ± 10.44; results indicated impairment in 75 cases (31.0%). PASAT score was correlated with several clusters involving the following regions: bilateral precuneus and posterior cingulate, bilateral caudate and putamen, and bilateral cerebellum. Voxel-based lesion symptom mapping showed no significant clusters. Region of interest–based analysis restricted to white matter regions revealed a correlation with the left cingulum, corpus callosum, bilateral corticospinal tracts, and right arcuate fasciculus. Correlations between PASAT scores and global volumes were weak.ConclusionPASAT score was associated with regional volumes of the posterior cingulate/precuneus and several subcortical structures, specifically the caudate, putamen, and cerebellum. This emphasises the role of both cortical and subcortical structures in cognitive functioning and information processing speed in patients with MS.

Brain tissue volumes and relaxation rates in multiple sclerosis: implications for cognitive impairment.

Both normal gray matter atrophy and brain tissue relaxation rates, in addition to total lesion volume, have shown significant correlations with cognitive test scores in multiple sclerosis (MS). Aim of the study was to assess the relative contributions of macro- and microstructural changes of both normal and abnormal brain tissues, probed, respectively, by their volumes and relaxation rates, to the cognitive status and physical disability of MS patients. MRI studies from 241 patients with relapsing-remitting MS were retrospectively analyzed by fully automated multiparametric relaxometric segmentation. Ordinal backward regression analysis was applied to the resulting volumes and relaxation rates of both normal (gray matter, normal-appearing white matter and CSF) and abnormal (T2-weighted lesions) brain tissues, controlling for age, sex and disease duration, to identify the main independent contributors to the cognitive status, as measured by the percentage of failed tests at a cognitive test battery (Rao's Brief Repeatable Battery and Stroop test, available in 186 patients), and to the physical disability, as assessed by the Expanded Disability Status Scale (EDSS). The R1 relaxation rate (a putative marker of tissue disruption) of the MS lesions appeared the single most significant contributor to cognitive impairment (p < 0.001). On the contrary, the EDSS appeared mainly affected by the decrease in R2 of the gray matter (p < 0.0001), (possibly influenced by cortical plaques, edema and inflammation). In RR-MS the tissue damage in white matter lesions appears the single main determinant of the cognitive status of patients, likely through disconnection phenomena, while the physical disability appears related to the involvement of gray matter.