Leriglitazone halts disease progression in adult patients with early cerebral adrenoleukodystrophy.

Cerebral adrenoleukodystrophy (CALD) is an X-linked rapidly progressive demyelinating disease leading to death usually within a few years. The standard of care is haematopoietic stem cell transplantation (HSCT), but many men are not eligible due to age, absence of a matched donor or lesions of the corticospinal tracts (CST). Based on the ADVANCE study showing that leriglitazone decreases the occurrence of CALD, we treated 13 adult CALD patients (19-67 years of age) either not eligible for HSCT (n = 8) or awaiting HSCT (n = 5). Patients were monitored every 3 months with standardized neurological scores, plasma biomarkers and brain MRI comprising lesion volumetrics and diffusion tensor imaging. The disease stabilized clinically and radiologically in 10 patients with up to 2 years of follow-up. Five patients presented with gadolinium enhancing CST lesions that all turned gadolinium negative and, remarkably, regressed in four patients. Plasma neurofilament light chain levels stabilized in all 10 patients and correlated with lesion load. The two patients who continued to deteriorate were over 60 years of age with prominent cognitive impairment. One patient died rapidly from coronavirus disease 2019. These results suggest that leriglitazone can arrest disease progression in adults with early-stage CALD and may be an alternative treatment to HSCT.

Volumetric growth rate of incidentally found meningiomas on immunotherapy.

PURPOSE: The expression of PD-L1 in high-grade meningiomas made it a potential target for immunotherapy research in refractory cases. Several prospective studies in this field are still on going. We sought to retrospectively investigate the effects of check-point inhibitors (CI) on meningiomas that had been naïve to either surgical or radiation approaches by following incidental meningiomas found during treatment with CI for various primary metastatic cancers. METHODS: We used the NYU Perlmutter Cancer Center Data Hub to find patients treated by CI for various cancers, who also had serial computerized-tomography (CT) or magnetic-resonance imaging (MRI) reports of intracranial meningiomas. Meningioma volumetric measurements were compared between the beginning and end of the CI treatment period. Patients treated with chemotherapy during this period were excluded. RESULTS: Twenty-five patients were included in our study, of which 14 (56%) were on CI for melanoma, 5 (20%) for non-small-cell lung cancer and others. CI therapies included nivolumab (n = 15, 60%), ipilimumab (n = 11, 44%) and pembrolizumab (n = 9, %36), while 9 (36%) were on ipilimumab/nivolumab combination. We did not find any significant difference between tumor volumes before and after treatment with CI (1.31 ± 0.46 vs. 1.34 ± 0.46, p=0.8, respectively). Among patients beyond 1 year of follow-up (n = 13), annual growth was 0.011 ± 0.011 cm3/year. Five patients showed minor volume reduction of 0.12 ± 0.10 cm3 (21 ± 6% from baseline). We did not find significant predictors of tumor volume reduction. CONCLUSION: Check-point inhibitors may impact the natural history of meningiomas. Additional research is needed to define potential clinical indications and treatment goals.

Eureka: objective assessment of the empty pelvis syndrome to measure volumetric changes in pelvic dead space following pelvic exenteration.

BACKGROUND: Large tissue defects following pelvic exenteration (PE) fill with fluid and small bowel, leading to the empty pelvis syndrome (EPS). EPS causes a constellation of complications including pelvic sepsis and reduced quality of life. EPS remains poorly defined and cannot be objectively measured. Pathophysiology of EPS is multifactorial, with increased pelvic dead space potentially important. This study aims to describe methodology to objectively measure volumetric changes relating to EPS. METHODS: The true pelvis is defined by the pelvic inlet and outlet. Within the true pelvis there is physiological pelvic dead space (PDS) between the peritoneal reflection and the inlet. This dead space is increased following PE and is defined as the exenteration pelvic dead space (EPD). EPD may be reduced with pelvic filling and the volume of filling is defined as the pelvic filling volume (PFV). PDS, EPD, and PFV were measured intraoperatively using a bladder syringe, and Archimedes' water displacement principle. RESULTS: A patient undergoing total infralevator PE had a PDS of 50 ml. A rectus flap rendered the pelvic outlet watertight. EPD was then measured as 540 ml. Therefore there was a 10.8-fold increase in true pelvis dead space. An omentoplasty was placed into the EPD, displacing 130 ml; therefore, PFV as a percentage of EPD was 24.1%. CONCLUSIONS: This is the first reported quantitative assessment of pathophysiological volumetric changes of pelvic dead space; these measurements may correlate to severity of EPS. PDS, EPD, and PFV should be amendable to assessment based on perioperative cross-sectional imaging, allowing for potential prediction of EPS-related outcomes.

Serum glial fibrillary acidic protein in natalizumab-treated relapsing-remitting multiple sclerosis: An alternative to neurofilament light.

BACKGROUND: There is a need in Relapsing-Remitting Multiple Sclerosis (RRMS) treatment for biomarkers that monitor neuroinflammation, neurodegeneration, treatment response, and disease progression despite treatment. OBJECTIVE: To assess the value of serum glial fibrillary acidic protein (sGFAP) as a biomarker for clinical disease progression and brain volume measurements in natalizumab-treated RRMS patients. METHODS: sGFAP and neurofilament light (sNfL) were measured in an observational cohort of natalizumab-treated RRMS patients at baseline, +3, +12, and +24 months and at the last sample follow-up (median 5.17 years). sGFAP was compared between significant clinical progressors and non-progressors and related to magnetic resonance imaging (MRI)-derived volumes of the whole brain, ventricle, thalamus, and lesion. The relationship between sGFAP and sNfL was assessed. RESULTS: A total of 88 patients were included, and 47.7% progressed. sGFAP levels at baseline were higher in patients with gadolinium enhancement (1.3-fold difference, p = 0.04) and decreased in 3 months of treatment (adj. p < 0.001). No association was found between longitudinal sGFAP levels and progressor status. sGFAP at baseline and 12 months was significantly associated with normalized ventricular (positively), thalamic (negatively), and lesion volumes (positively). Baseline and 12-month sGFAP predicted annualized ventricle volume change rate after 1 year of treatment. sGFAP correlated with sNfL at baseline (p < 0.001) and last sample follow-up (p < 0.001) but stabilized earlier. DISCUSSION: sGFAP levels related to MRI markers of neuroinflammation and neurodegeneration.

Automated Deep Learning Artificial Intelligence Tool for Spleen Segmentation on CT: Defining Volume-Based Thresholds for Splenomegaly.

BACKGROUND. Splenomegaly historically has been assessed on imaging by use of potentially inaccurate linear measurements. Prior work tested a deep learning artificial intelligence (AI) tool that automatically segments the spleen to determine splenic volume. OBJECTIVE. The purpose of this study is to apply the deep learning AI tool in a large screening population to establish volume-based splenomegaly thresholds. METHODS. This retrospective study included a primary (screening) sample of 8901 patients (4235 men, 4666 women; mean age, 56 ± 10 [SD] years) who underwent CT colonoscopy (n = 7736) or renal donor CT (n = 1165) from April 2004 to January 2017 and a secondary sample of 104 patients (62 men, 42 women; mean age, 56 ± 8 years) with end-stage liver disease who underwent contrast-enhanced CT performed as part of evaluation for potential liver transplant from January 2011 to May 2013. The automated deep learning AI tool was used for spleen segmentation, to determine splenic volumes. Two radiologists independently reviewed a subset of segmentations. Weight-based volume thresholds for splenomegaly were derived using regression analysis. Performance of linear measurements was assessed. Frequency of splenomegaly in the secondary sample was determined using weight-based volumetric thresholds. RESULTS. In the primary sample, both observers confirmed splenectomy in 20 patients with an automated splenic volume of 0 mL; confirmed incomplete splenic coverage in 28 patients with a tool output error; and confirmed adequate segmentation in 21 patients with low volume (< 50 mL), 49 patients with high volume (> 600 mL), and 200 additional randomly selected patients. In 8853 patients included in analysis of splenic volumes (i.e., excluding a value of 0 mL or error values), the mean automated splenic volume was 216 ± 100 [SD] mL. The weight-based volumetric threshold (expressed in milliliters) for splenomegaly was calculated as (3.01 × weight [expressed as kilograms]) + 127; for weight greater than 125 kg, the splenomegaly threshold was constant (503 mL). Sensitivity and specificity for volume-defined splenomegaly were 13% and 100%, respectively, at a true craniocaudal length of 13 cm, and 78% and 88% for a maximum 3D length of 13 cm. In the secondary sample, both observers identified segmentation failure in one patient. The mean automated splenic volume in the 103 remaining patients was 796 ± 457 mL; 84% (87/103) of patients met the weight-based volume-defined splenomegaly threshold. CONCLUSION. We derived a weight-based volumetric threshold for splenomegaly using an automated AI-based tool. CLINICAL IMPACT. The AI tool could facilitate large-scale opportunistic screening for splenomegaly.

The impact of neurological performance and volumetrics on overall survival in brain metastasis in colorectal cancer: a retrospective single-center case series.

BACKGROUND: Brain metastasis (BM) of colorectal cancer is a disease with a poor prognosis of only a few months survival. However, it is difficult to estimate the individual prognosis of each patient due to the lack of definitive prognosis parameters. The number of metastases and the Karnofsky performance score are known predictors for survival. We investigated whether or not the neurological performance score and the tumor volumetrics are equally suitable predictors for survival. DESIGN: All patients with histologically diagnosed BM linked to colorectal cancer between 2012 and March 2020 were reviewed. The Medical Research Council Neurological Performance Score was used to quantify neurological performance. Univariate analysis with Kaplan-Meier estimate and log-rank test was performed. Survival prediction and multivariate analysis were performed employing Cox proportional hazard regression. RESULTS: Twenty-five patients were included in our analysis with an overall survival of 4.9 months after surgery of the BM. Survival decreased in the univariate analysis with increasing postoperative neurological performance score, low Karnofsky performance score, absence of radiation therapy and radiation therapy modality. The neurological performance score is a reliable scoring parameter for estimating the prognostic course analogous to the Karnofsky performance score. Neither preoperative nor post resection residual tumor volume had any impact on overall survival in our small cohort. CONCLUSION: Our data suggest that the postoperative neurological performance is a valuable prognostic factor for colorectal cancer patients with BM. Tumor volumetrics show no correlation to survival. Further investigations with a larger number of cases are mandatory.

Neurofilament-light and contactin-1 association with long-term brain atrophy in natalizumab-treated relapsing-remitting multiple sclerosis.

BACKGROUND: Despite highly effective treatment strategies for patients with relapsing-remitting multiple sclerosis (RRMS), long-term neurodegeneration and disease progression are often considerable. Accurate blood-based biomarkers that predict long-term neurodegeneration are lacking. OBJECTIVE: To assess the predictive value of serum neurofilament-light (sNfL) and serum contactin-1 (sCNTN1) for long-term magnetic resonance imaging (MRI)-derived neurodegeneration in natalizumab-treated patients with RRMS. METHODS: sNfL and sCNTN1 were measured in an observational cohort of natalizumab-treated patients with RRMS at baseline (first dose) and at 3 months, Year 1, Year 2, and last follow-up (median = 5.2 years) of treatment. Disability progression was quantified using "EDSS-plus" criteria. Neurodegeneration was measured by calculating annualized percentage brain, ventricular, and thalamic volume change (PBVC, VVC, and TVC, respectively). Linear regression analysis was performed to identify longitudinal predictors of neurodegeneration. RESULTS: In total, 88 patients (age = 37 ± 9 years, 75% female) were included, of whom 48% progressed. Year 1 sNfL level (not baseline or 3 months) was associated with PBVC (standardized (std.) ß = -0.26, p = 0.013), VVC (standardized ß = 0.36, p < 0.001), and TVC (standardized ß = -0.24, p = 0.02). For sCNTN1, only 3-month level was associated with VVC (standardized ß = -0.31, p = 0.002). CONCLUSION: Year 1 (but not baseline) sNfL level was predictive for long-term brain atrophy in patients treated with natalizumab. sCNTN1 level did not show a clear predictive value.

Ipsilesional volume loss of basal ganglia and thalamus is associated with poor hand function after ischemic perinatal stroke.

BACKGROUND: Perinatal stroke (PS) is the leading cause of hemiparetic cerebral palsy (CP). Involvement of the corticospinal tract on neonatal magnetic resonance imaging (MRI) is predictive of motor outcome in patients with hemiparetic CP. However, early MRI is not available in patients with delayed presentation of PS and prediction of hemiparesis severity remains a challenge. AIMS: To evaluate the volumes of the basal ganglia, amygdala, thalamus, and hippocampus following perinatal ischemic stroke in relation to hand motor function in children with a history of PS and to compare the volumes of subcortical structures in children with PS and in healthy controls. METHODS: Term born PS children with arterial ischemic stroke (AIS) (n = 16) and with periventricular venous infarction (PVI) (n = 18) were recruited from the Estonian Pediatric Stroke Database. MRI was accuired during childhood (4-18 years) and the volumes of the basal ganglia, thalamus, amygdala and hippocampus were calculated. The results of stroke patients were compared to the results of 42 age- and sex-matched healthy controls. Affected hand function was evaluated by Assisting Hand Assessment (AHA) and classified by the Manual Ability Classification System (MACS). RESULTS: Compared to the control group, children with AIS had smaller volumes of the ipsi- and contralesional thalami, ipsilesional globus pallidus, nucleus accumbens and hippocampus (p < 0.005). Affected hand function in children with AIS was correlated with smaller ipsilesional thalamus, putamen, globus pallidus, hippocampus, amygdala and contralesional amygdala (r > 0.5; p < 0.05) and larger volume of the contralesional putamen and hippocampus (r < - 0.5; p < 0.05). In children with PVI, size of the ipsilesional caudate nucleus, globus pallidus, thalamus (p ≤ 0.001) and hippocampus (p < 0.03) was smaller compared to controls. Smaller volume of the ipsi- and contralesional thalami and ipsilesional caudate nucleus was correlated with affected hand function (r > 0.55; p < 0.05) in children with PVI. CONCLUSIONS: Smaller volume of ipsilesional thalamus was associated with poor affected hand function regardless of the perinatal stroke subtype. The pattern of correlation between hand function and volume differences in the other subcortical structures varied between children with PVI and AIS. Evaluation of subcortical structures is important in predicting motor outcome following perinatal stroke.

Efficiency of a deep learning-based artificial intelligence diagnostic system in spontaneous intracerebral hemorrhage volume measurement.

BACKGROUND: Accurate measurement of hemorrhage volume is critical for both the prediction of prognosis and the selection of appropriate clinical treatment after spontaneous intracerebral hemorrhage (ICH). This study aimed to evaluate the performance and accuracy of a deep learning-based automated segmentation algorithm in segmenting spontaneous intracerebral hemorrhage (ICH) volume either with or without intraventricular hemorrhage (IVH) extension. We compared this automated pipeline with two manual segmentation techniques. METHODS: We retrospectively reviewed 105 patients with acute spontaneous ICH. Depending on the presence of IVH extension, patients were divided into two groups: ICH without (n = 56) and with IVH (n = 49). ICH volume of the two groups were segmented and measured using a deep learning-based artificial intelligence (AI) diagnostic system and computed tomography-based planimetry (CTP), and the ABC/2 score were used to measure hemorrhage volume in the ICH without IVH group. Correlations and agreement analyses were used to analyze the differences in volume and length of processing time among the three segmentation approaches. RESULTS: In the ICH without IVH group, the ICH volumes measured using AI and the ABC/2 score were comparable to CTP segmentation. Strong correlations were observed among the three segmentation methods (r = 0.994, 0.976, 0.974; P < 0.001; concordance correlation coefficient [CCC] = 0.993, 0.968, 0.967). But the absolute error of the ICH volume measured by the ABC/2 score was greater than that of the algorithm (P < 0.05). In the ICH with IVH group, there is no significant differences were found between algorithm and CTP(P = 0.614). The correlation and agreement between CTP and AI were strong (r = 0.996, P < 0.001; CCC = 0.996). The AI segmentation took a significantly shorter amount of time than CTP (P < 0.001), but was slightly longer than ABC/2 score technique (P = 0.002). CONCLUSIONS: The deep learning-based AI diagnostic system accurately quantified volumes of acute spontaneous ICH with high fidelity and greater efficiency compared to the CTP measurement and more accurately than the ABC/2 scores. We believe this is a promising tool to help physicians achieve precise ICH quantification in practice.

Systemic inflammation moderates the association of prior concussion with hippocampal volume and episodic memory in high school and collegiate athletes.

BACKGROUND: There is a need to determine why prior concussion has been associated with adverse outcomes in some retired and active athletes. We examined whether serum inflammatory markers moderate the associations of prior concussion with hippocampal volumes and neurobehavioral functioning in active high school and collegiate athletes. METHODS: Athletes (N = 201) completed pre-season clinical testing and serum collection (C-reactive protein [CRP]; Interleukin-6 [IL]-6; IL-1 receptor antagonist [RA]) and in-season neuroimaging. Linear mixed-effects models examined associations of prior concussion with inflammatory markers, self-reported symptoms, neurocognitive function, and hippocampal volumes. Models examined whether inflammatory markers moderated associations of concussion history and hippocampal volume and/or clinical measures. RESULTS: Concussion history was significantly associated with higher symptom severity, p = 0.012, but not hippocampal volume or inflammatory markers (ps > 0.05). A significant interaction of prior concussion and CRP was observed for hippocampal volume, p = 0.006. Follow-up analyses showed that at high levels of CRP, athletes with two or more prior concussions had smaller hippocampal volume compared to athletes without prior concussion, p = 0.008. There was a significant interaction between prior concussion and levels of IL-1RA on memory scores, p = 0.044, i.e., at low levels of IL-1RA, athletes with two or more concussions had worse memory performance than those without prior concussion (p = 0.014). CONCLUSION: Findings suggest that certain markers of systemic inflammation moderate the association between prior concussion and hippocampal volume and episodic memory performance. Current findings highlight potential markers for predicting at-risk individuals and identify therapeutic targets for mitigating the long-term adverse consequences of cumulative concussion.

Intraclass Correlations of Measured Magnetic Resonance Imaging Volumes of Laser Interstitial Thermal Therapy-Treated High-Grade Gliomas.

BACKGROUND AND OBJECTIVES: Laser interstitial thermal therapy (LITT) is a minimally invasive therapeutic option for the treatment of brain tumors. Previous studies have quantitatively followed the ablated volumes of high-grade gliomas. Reported treatment volumes range from 28% to 100%, with no reported interobserver analysis. Because these volumes are subjectively measured, it is necessary to establish concordance between clinicians. STUDY DESIGN/MATERIALS AND METHODS: Utilizing Brainlab tumor analysis software (Brainlab, Munich, Germany), five physician users traced out tumor volumes slice-by-slice on 10 treated tumors in eight patients. The participants were briefed with specific instructions and a demonstration on how to trace the enhancing borders of the tumor slice-by-slice. Volumes automatically calculated by the Brainlab software included preoperative, intraoperative ablation and postoperative enhancing volumes. Data regarding size, cystic appearance, pathology, previous surgery, and demographics were included. RESULTS: The intraclass correlation coefficient (ICC) for preoperative, intraoperative, and postoperative volumes was 0.92 (95% confidence interval, [CI] 0.81-0.97), 0.90 (0.77-0.96), and 0.89 (0.74-0.96), respectively. The overall ICC was 0.72 (0.50-0.87). ICC comparisons were also made for each pair of readers (neuroradiologist, neuro-oncologist, senior neurosurgery resident, neurosurgery junior resident) which resulted in pretreatment ICC scores of 0.97, 0.91, 0.66, 0.94; intratreatment scores of 0.97, 0.78, 0.90, 0.96; and posttreatment scores of 0.96, 0.81, 0.89, and 0.87. A Bland-Altman plot was also used to assess the differences in volumes. CONCLUSIONS: The ICC gives a composite of the consistency of measurements made by multiple observers measuring the same quantity. The overall ICC of 0.72 means there is good correlation between observers in our study between measured volumes. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Magnetic resonance-guided laser interstitial thermal therapy for the treatment of non-lesional insular epilepsy in pediatric patients: thermal dynamic and volumetric factors influencing seizure outcomes.

PURPOSE: To investigate the safety and efficacy of stereoelectroencephalography (sEEG) directed magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) in medically refractory insular epilepsy in pediatric patients, define the relationship between ablation volumes and seizure control, and analyze the relationship between thermal energy and ablation volumes. METHODS: A single-institution, retrospective review of pediatric patients with insular epilepsy who underwent sEEG directed MRgLITT over a 10-month period was performed. Perioperative, imaging, and outcome data were analyzed. Seizure outcomes were determined based on Engel score (Engel I versus Engel II-IV). Insula and ablation volumes were measured, and the proportion of insula volume ablated was calculated. Thermal energy was calculated in joules. RESULTS: Four patients underwent sEEG directed MRgLITT of insular epileptogenic foci. The ablation volume was higher in patients with Engel I outcome (3.93 cm3) compared to Engel II-IV outcome (1.02 cm3). The proportion of ablation to insula volume was lowest in patients with Engel II-IV outcome (25.09%). The mean energy requirement to create a unit volume of ablation in the insula is 1205.86 J. A linear trend was noted between thermal ablation energy and ablation volume (R2 = 0.884). Over a mean follow-up period of 104 days, three patients were seizure-free (Engel I), and one patient saw significant improvement in seizure frequency (Engel III). CONCLUSIONS: The proportion of insula ablated, as well as the volume of ablation, are related to seizure outcome with increasing ablation volumes corresponding to improved seizure control. Further analysis of insula laser ablation thermal dynamics and volumes is needed.

Case report: neuroimaging analysis of pediatric ADHD-related symptoms secondary to hypoxic brain injury.

A 2-year-old male pediatric patient experienced a partial occlusion of the internal carotid and subsequent asphyxiation resulting in hypoxic brain injury that was later misdiagnosed as primary attention deficient hyperactivity disorder (ADHD). Imaging analyses using diffusion tensor imaging (DTI), positron emission tomography (PET), and magnetic resonance imaging (MRI) quantitative volumetrics (QV) were used nine years following the incident to identify whether his development of ADHD is of a primary heritability or secondary hypoxic brain injury sequelae. The patient's DTI analysis generated decreases in fractional anisotropy (FA) values in the anterior corpus callosum, bilateral internal capsule, and hippocampus. Decreases in FA are seen in ADHD patients, but the degree of FA decrease in the patient under study is several orders of magnitude greater than in ADHD patients. Also, not normally observed in ADHD patients were decreases in the metabolism of the orbitofrontal cortex, anterior cingulate, left anterior insular cortex, and left striatum. Additionally, QV showed enlargements of various regions of the brain including the amygdala which is often cited in the literature to be reduced in ADHD patients. The diagnosis of this patient despite having non-characteristic neuroimaging data suggests a unique specificity of the hypoxic injury to the development of a secondary hypoxic brain injury caused ADHD.

A harmonized longitudinal biomarkers and cognition database for assessing the natural history of preclinical Alzheimer's disease from young adulthood and for designing prevention trials.

INTRODUCTION: Large longitudinal biomarkers database focusing on middle age is needed for Alzheimer's disease (AD) prevention. METHODS: Data for cerebrospinal fluid analytes, molecular imaging of cerebral fibrillar ß-amyloid with positron emission tomography, magnetic resonance imaging-based brain structures, and clinical/cognitive outcomes were harmonized across eight AD biomarker studies. Statistical power was estimated. RESULTS: The harmonized database included 7779 participants with clinical/cognitive data: 3542 were 18∼65 years at the baseline, 5865 had longitudinal cognitive data for a median of 4.7 years, 2473 participated in the cerebrospinal fluid studies (906 had longitudinal data), 2496 participated in the magnetic resonance imaging studies (1283 had longitudinal data), and 1498 participated in the positron emission tomography amyloid studies (849 had longitudinal data). The database provides adequate power for detecting early biomarker changes, and demonstrates the feasibility of AD prevention trials on middle-aged individuals. DISCUSSION: The harmonized database is an optimum resource to design AD prevention trials decades before symptomatic onset.

Left ventricular function and regional strain with subtly-tagged steady-state free precession feature tracking.

PURPOSE: To provide regional strain and ventricular volume from a single acquisition, using subtly tagged steady-state free precession (SubTag SSFP) feature tracking. MATERIALS AND METHODS: The effects on regional strain of tag strength in gradient recalled echo (GRE) tagging, flip angle in untagged balanced SSFP, and both in SubTag SSFP were examined in the mid left ventricle of 15 healthy volunteers at 3T. Optimal parameters were determined from varying both tag strength and SSFP flip angle using full tag saturation GRE as the reference standard. SubTag SSFP was acquired in 15 additional healthy volunteers for whole-heart volume and strain assessment using the optimized parameters. Values measured by two image analysts were compared to clinical reference standards from untagged SSFP (volumes) and GRE tagging (strains). RESULTS: Regional strain accuracy was maintained with decreasing total tagging flip angle (ß); less than 3% differences for ß ≥ 26°. For untagged SSFP flip angle (α), whole-wall strain differences became statistically significant when α < 40°. A SubTag SSFP acquisition with α = 40° and ß = 46° showed the best combination of tagging strength, blood-myocardial contrast, and tag persistence at end-systole for regional strain estimation. SubTag SSFP also showed excellent agreement with untagged SSFP for volumetrics (percent difference: end-diastolic volume = 0.6%, end-systolic volume = 0.4%, stroke volume = 1.2%, ejection fraction = 0.6%, mass = 1.1%). CONCLUSION: Feature tracking for regional myocardial strain assessment is dependent on image features, mainly the tag strength, persistence, and image contrast. SubTag SSFP balances these criteria to provide accurate regional strain and volumetric assessment in a single acquisition. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2018;47:787-797.

Effect of lapatinib on meningioma growth in adults with neurofibromatosis type 2.

INTRODUCTION: Epidermal growth factor receptors EGFR and ErbB2 are overexpressed in schwannomas and meningiomas. Preclinical and clinical data indicate that lapatinib, an EGFR/ErbB2 inhibitor, has antitumor activity against vestibular schwannomas in neurofibromatosis type 2 (NF2) patients. Its antitumor activity against meningiomas, however, is unknown. METHODS: We conducted a retrospective review of patients with NF2 and progressive vestibular schwannomas treated on a phase 2 clinical trial with lapatinib (NCT00973739). We included patients with at least one volumetrically measurable meningioma (> 0.5 cm3) who received at least five 28-day courses of treatment. Patients received lapatinib 1500 mg daily. Meningioma response was assessed using 3-dimensional MRI volumetrics. Progressive meningioma growth and response were defined as + 20 and - 20% change in tumor volume from baseline, respectively. Off-treatment was defined as any period > 5 months without lapatinib. RESULTS: Eight patients (ages: 20-58 years) who met criteria had 17 evaluable meningiomas with a combined volume of 61.35 cc at baseline, 61.17 cc during treatment, and 108.86 cc (+ 77.44% change) off-treatment, p = 0.0033. Median time on-treatment and off-treatment was 15.5 and 16.7 months, respectively. On-treatment mean and median annualized growth rates were 10.67 and 1.32%, respectively. Off-treatment mean and median annualized growth rates were 20.05 and 10.42%, respectively. The best volumetric response was - 26.1% after 23 months on lapatinib. Two tumors increased > 20% volumetrically on-treatment, compared to eight tumors off-treatment. CONCLUSIONS: These data suggest that lapatinib may have growth-inhibitory effects on meningiomas in NF2 patients, and support prospective studies of lapatinib for NF2 patients with progressive meningiomas.

Erythropoietin and Brain Magnetic Resonance Imaging Findings in Hypoxic-Ischemic Encephalopathy: Volume of Acute Brain Injury and 1-Year Neurodevelopmental Outcome.

In the Neonatal Erythropoietin and Therapeutic Hypothermia Outcomes study, 9/20 erythropoietin-treated vs 12/24 placebo-treated infants with hypoxic-ischemic encephalopathy had acute brain injury. Among infants with acute brain injury, the injury volume was lower in the erythropoietin than the placebo group (P = .004). Higher injury volume correlated with lower 12-month neurodevelopmental scores. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01913340.

Comparison of One-Dimensional and Volumetric Computed Tomography Measurements of Injected-Water Phantoms.

The goal of this study was to compare volumetric analysis in computed tomography (CT) with the length measurement prescribed by the Response Evaluation Criteria in Solid Tumors (RECIST) for a system with known mass and unknown shape. We injected 2 mL to 4 mL of water into vials of sodium polyacrylate and into disposable diapers. Volume measurements of the sodium polyacrylate powder were able to predict both mass and proportional changes in mass within a 95 % prediction interval of width 12 % and 16 %, respectively. The corresponding figures for RECIST were 102 % and 82 %.

Effect of non-alcoholic liver disease on recurrence rate and liver regeneration after liver resection for colorectal liver metastases.

BACKGROUND: Resection of metastases is the only potential cure for patients with liver metastasis from colorectal cancer (crc-lm). But despite an improved overall 5-year survival, the recurrence rate is still as high as 60%. Non-alcoholic fatty liver disease (nafld) can decrease the liver's capacity to regenerate after resection and might also affect cancer recurrence, potentially by elevating transforming growth factor ß, levels of specific metalloproteinases, and oxidative stress. The objective of the present work was to determine the effect of the histologic features of nafld on cancer recurrence and liver regeneration. METHODS: This retrospective analysis considered 60 patients who underwent an R0 hepatectomy for crc-lm. Volumetric analysis of the liver was calculated using axial view, portovenous phase, 2.5 mm thickness, multiphasic computed tomography images taken before and after surgery. The histologic features of nafld (steatosis, inflammation, and ballooning) were scored using the nafld activity score, and the degree of fibrosis was determined. RESULTS: The hepatic recurrence rate was 38.33%. Median overall survival duration was 56 months. Median disease-free survival duration was 14 months, and median hepatic disease-free survival duration was 56 months. Multivariate analysis revealed significant correlations of hepatic disease-free survival with hepatocyte ballooning (p = 0.0009), lesion diameter (p = 0.014), and synchronous disease (p = 0.006). Univariate and multivariate analyses did not reveal any correlation with degree of steatosis or recurrence rate. CONCLUSIONS: This study reveals an important potential negative effect of hepatocyte ballooning on hepatic disease-free survival.

Human immunodeficiency virus has similar effects on brain volumetrics and cognition in males and females.

Most studies that have examined neuropsychological impairments associated with human immunodeficiency virus (HIV) have focused on males, yet females represent one of the largest groups of newly infected patients. Further, few studies have examined neuropsychological performance and neuroimaging outcomes among females compared to males in the modern era of highly active anti-retroviral therapy (HAART). The present study investigated neuropsychological performance and brain volumetrics among HIV+ males (n = 93) and females (n = 44) on stable HAART compared to HIV seronegative (HIV-) males (n = 42) and females (n = 49). Results revealed a significant effect of HIV on neuropsychological performance and neuroimaging measures. An effect of gender, independent of HIV status, was also observed for neuroimaging measures but not neuropsychological performance. Additionally, no significant differences in neuropsychological performance or brain volumetrics were seen between HIV+ males and females. No significant interaction was observed between HIV and gender on either neuropsychological or neuroimaging indices. Our results suggest that both HIV+ males and females treated with HAART experience similar outcomes in terms of brain integrity.