Charles R Joseph, Alec Kreilach, Victoria Ashley Reyna, Thomas Ashton Kepler, Brittany Viola Taylor, Jubin Kang, Dallas McCorkle, Nicholas L Rider
{"title":"Utilizing Reduced Labeled Proton Clearance to Identify Preclinical Alzheimer Disease with 3D ASL MRI.","authors":"Charles R Joseph, Alec Kreilach, Victoria Ashley Reyna, Thomas Ashton Kepler, Brittany Viola Taylor, Jubin Kang, Dallas McCorkle, Nicholas L Rider","doi":"10.1159/000530980","DOIUrl":null,"url":null,"abstract":"<p><p>Addressing the seminal pathophysiology in Alzheimer disease (AD) is the next logical focus for effective intervention, given the initial disappointing and more recent possibly encouraging results of monoclonal antibody trials. Endothelial cell dysfunction-induced blood-brain barrier leak with associated prolonged capillary mean transit time (cMTT) and glymphatic outflow dysfunction is the most proximal events in the degeneration cascade. Sensitive and reproducible markers are required to both identify early disease and assess future treatment trial outcomes. Two participants, with mild cognitive impairment (MCI) and one with AD, were evaluated clinically prior to MRI in this small case series report. From seven 3D turbo gradient and spin echo (TGSE) pulsed arterial spin echo (PASL) MRI sequences six homologous region of interest in bitemporal, bifrontal, and biparietal lobes for each sequence were examined and plotted against time. By choosing late perfusion times during cMTT phase of perfusion linear analysis of signal decay could be utilized. A reference axial FLAIR sequence was also obtained. Slope of the linear analysis correlated to the rate of labeled proton clearance with reduced clearance occurring in AD participants compared to normal participants in our previous study. Whether similar differences in clearance rate extend to either MCI or early AD was investigated. Participants were categorized by clinical phenotype before MRI and compared to previously published phenotype cohorts: <i>n</i> = 18 normal/healthy, <i>n</i> = 6 AD, <i>n</i> = 3 MCI. Significant differences in labeled proton clearance rates between AD and MCI/control phenotypes within bilateral temporal lobes (left <i>p</i> = 0.004, right <i>p</i> = 0.002) and within bilateral frontal lobes AD versus controls (left <i>p</i> = 0.001, right <i>p</i> = 0.008) and AD versus MCI (left <i>p</i> = 0.001, right <i>p</i> = 0.001) were found. This noninvasive MRI technique has potential for identifying MCI transition to AD.</p>","PeriodicalId":9639,"journal":{"name":"Case Reports in Neurology","volume":"15 1","pages":"177-186"},"PeriodicalIF":0.6000,"publicationDate":"2023-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10603764/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Case Reports in Neurology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1159/000530980","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/1/1 0:00:00","PubModel":"eCollection","JCR":"Q4","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Addressing the seminal pathophysiology in Alzheimer disease (AD) is the next logical focus for effective intervention, given the initial disappointing and more recent possibly encouraging results of monoclonal antibody trials. Endothelial cell dysfunction-induced blood-brain barrier leak with associated prolonged capillary mean transit time (cMTT) and glymphatic outflow dysfunction is the most proximal events in the degeneration cascade. Sensitive and reproducible markers are required to both identify early disease and assess future treatment trial outcomes. Two participants, with mild cognitive impairment (MCI) and one with AD, were evaluated clinically prior to MRI in this small case series report. From seven 3D turbo gradient and spin echo (TGSE) pulsed arterial spin echo (PASL) MRI sequences six homologous region of interest in bitemporal, bifrontal, and biparietal lobes for each sequence were examined and plotted against time. By choosing late perfusion times during cMTT phase of perfusion linear analysis of signal decay could be utilized. A reference axial FLAIR sequence was also obtained. Slope of the linear analysis correlated to the rate of labeled proton clearance with reduced clearance occurring in AD participants compared to normal participants in our previous study. Whether similar differences in clearance rate extend to either MCI or early AD was investigated. Participants were categorized by clinical phenotype before MRI and compared to previously published phenotype cohorts: n = 18 normal/healthy, n = 6 AD, n = 3 MCI. Significant differences in labeled proton clearance rates between AD and MCI/control phenotypes within bilateral temporal lobes (left p = 0.004, right p = 0.002) and within bilateral frontal lobes AD versus controls (left p = 0.001, right p = 0.008) and AD versus MCI (left p = 0.001, right p = 0.001) were found. This noninvasive MRI technique has potential for identifying MCI transition to AD.
期刊介绍:
This new peer-reviewed online-only journal publishes original case reports covering the entire spectrum of neurology. Clinicians and researchers are given a tool to disseminate their personal experience to a wider public as well as to review interesting cases encountered by colleagues all over the world. To complement the contributions supplementary material is welcomed. The reports are searchable according to the key words supplied by the authors; it will thus be possible to search across the entire growing collection of case reports with universally used terms, further facilitating the retrieval of specific information. Following the open access principle, the entire contents can be retrieved at no charge, guaranteeing easy access to this valuable source of anecdotal information at all times.