Pictorial review of multiparametric MRI in bladder urothelial carcinoma with variant histology: pearls and pitfalls.

Bladder cancer (BC), predominantly comprising urothelial carcinomas (UCs), ranks as the tenth most common cancer worldwide. UCs with variant histology (variant UC), including squamous differentiation, glandular differentiation, plasmacytoid variant, micropapillary variant, sarcomatoid variant, and nested variant, accounting for 5-10% of cases, exhibit more aggressive and advanced tumor characteristics compared to pure UC. The Vesical Imaging-Reporting and Data System (VI-RADS), established in 2018, provides guidelines for the preoperative evaluation of muscle-invasive bladder cancer (MIBC) using multiparametric magnetic resonance imaging (mpMRI). This technique integrates T2-weighted imaging (T2WI), dynamic contrast-enhanced (DCE)-MRI, and diffusion-weighted imaging (DWI) to distinguish MIBC from non-muscle-invasive bladder cancer (NMIBC). VI-RADS has demonstrated high diagnostic performance in differentiating these two categories for pure UC. However, its accuracy in detecting muscle invasion in variant UCs is currently under investigation. These variant UCs are associated with a higher likelihood of disease recurrence and require precise preoperative assessment and immediate surgical intervention. This review highlights the potential value of mpMRI for different variant UCs and explores the clinical implications and prospects of VI-RADS in managing these patients, emphasizing the need for careful interpretation of mpMRI examinations including DCE-MRI, particularly given the heterogeneity and aggressive nature of variant UCs. Additionally, the review addresses the fundamental MRI reading procedures, discusses potential causes of diagnostic errors, and considers future directions in the use of artificial intelligence and radiomics to further optimize the bladder MRI protocol.

Phase I/II Study of a Vascular Endothelial Growth Factor Receptor Vaccine in Patients With NF2-Related Schwannomatosis.

PURPOSE: The humanized antivascular endothelial growth factor (VEGF) antibody bevacizumab (Bev) is efficacious for the treatment of NF2-related schwannomatosis (NF2), previously known as neurofibromatosis type 2. This study evaluated the safety and efficacy of a VEGF receptor (VEGFR) vaccine containing VEGFR1 and VEGFR2 peptides in patients with NF2 with progressive schwannomas (jRCTs031180184). MATERIALS AND METHODS: VEGFR1 and VEGFR2 peptides were injected subcutaneously into infra-axillary and inguinal regions, once a week for 4 weeks and then once a month for 4 months. The primary end point was safety. Secondary end points included tolerability, hearing response, imaging response, and immunologic response. RESULTS: Sixteen patients with NF2 with progressive schwannomas completed treatment and were assessed. No severe vaccine-related adverse events occurred. Among the 13 patients with assessable hearing, word recognition score improved in five patients at 6 months and two at 12 months. Progression of average hearing level of pure tone was 0.168 dB/mo during the year of treatment period, whereas long-term progression was 0.364 dB/mo. Among all 16 patients, a partial response was observed in more than one schwannoma in four (including one in which Bev had not been effective), minor response in 5, and stable disease in 4. Both VEGFR1-specific and VEGFR2-specific cytotoxic T lymphocytes (CTLs) were induced in 11 patients. Two years after vaccination, a radiologic response was achieved in nine of 20 assessable schwannomas. CONCLUSION: This study demonstrated the safety and preliminary efficacy of VEGFR peptide vaccination in patients with NF2. Memory-induced CTLs after VEGFR vaccination may persistently suppress tumor progression.

Amyloid-ß prediction machine learning model using source-based morphometry across neurocognitive disorders.

Previous studies have developed and explored magnetic resonance imaging (MRI)-based machine learning models for predicting Alzheimer's disease (AD). However, limited research has focused on models incorporating diverse patient populations. This study aimed to build a clinically useful prediction model for amyloid-beta (Aß) deposition using source-based morphometry, using a data-driven algorithm based on independent component analyses. Additionally, we assessed how the predictive accuracies varied with the feature combinations. Data from 118 participants clinically diagnosed with various conditions such as AD, mild cognitive impairment, frontotemporal lobar degeneration, corticobasal syndrome, progressive supranuclear palsy, and psychiatric disorders, as well as healthy controls were used for the development of the model. We used structural MR images, cognitive test results, and apolipoprotein E status for feature selection. Three-dimensional T1-weighted images were preprocessed into voxel-based gray matter images and then subjected to source-based morphometry. We used a support vector machine as a classifier. We applied SHapley Additive exPlanations, a game-theoretical approach, to ensure model accountability. The final model that was based on MR-images, cognitive test results, and apolipoprotein E status yielded 89.8% accuracy and a receiver operating characteristic curve of 0.888. The model based on MR-images alone showed 84.7% accuracy. Aß-positivity was correctly detected in non-AD patients. One of the seven independent components derived from source-based morphometry was considered to represent an AD-related gray matter volume pattern and showed the strongest impact on the model output. Aß-positivity across neurological and psychiatric disorders was predicted with moderate-to-high accuracy and was associated with a probable AD-related gray matter volume pattern. An MRI-based data-driven machine learning approach can be beneficial as a diagnostic aid.

The Role of Genetic Analysis in Distinguishing Multifocal and Multicentric Glioblastomas: An Illustrative Case.

Introduction: Glioblastomas can manifest as multiple, simultaneous, noncontiguous lesions. We genetically analyzed multiple glioblastomas and discuss their etiological origins in this report. Case Presentation: We present the case of a 47-year-old woman who presented with memory impairment and left partial paralysis. Radiographic imaging revealed three apparently noncontiguous lesions in the right temporal and parietal lobes extending into the corpus callosum, leading to diagnosis of multicentric glioblastomas. All three lesions were excised. Genetic analysis of the lesions revealed a TERT promoter C228T mutation, a roughly equivalent amplification of EGFR, and homozygous deletion of CDKN2A/B exclusively in the two contrast-enhanced lesions. Additionally, the contrast-enhanced lesions exhibited the same two-base pair mutations of PTEN, whereas the non-enhanced lesion showed a partially distinct 13-base pair mutation. The other genetic characteristics were consistent. Rather than each having arisen de novo, we believe that they had developed by infiltration and are therefore best classified as multifocal glioblastomas. Conclusion: Our findings underscore anew the possibility of infiltration by glioblastomas, even within regions devoid of signal alterations on T2-weighted images or fluid-attenuated inversion recovery images. Genetic analysis can play a crucial role in differentiating whether multiple glioblastomas are multifocal or multicentric.

Performance of plasma Aß42/40, measured using a fully automated immunoassay, across a broad patient population in identifying amyloid status.

BACKGROUND: Plasma biomarkers have emerged as promising screening tools for Alzheimer's disease (AD) because of their potential to detect amyloid ß (Aß) accumulation in the brain. One such candidate is the plasma Aß42/40 ratio (Aß42/40). Unlike previous research that used traditional immunoassay, recent studies that measured plasma Aß42/40 using fully automated platforms reported promising results. However, its utility should be confirmed using a broader patient population, focusing on the potential for early detection. METHODS: We recruited 174 participants, including healthy controls (HC) and patients with clinical diagnoses of AD, frontotemporal lobar degeneration, dementia with Lewy bodies/Parkinson's disease, mild cognitive impairment (MCI), and others, from a university memory clinic. We examined the performance of plasma Aß42/40, measured using the fully automated high-sensitivity chemiluminescence enzyme (HISCL) immunoassay, in detecting amyloid-positron emission tomography (PET)-derived Aß pathology. We also compared its performance with that of Simoa-based plasma phosphorylated tau at residue 181 (p-tau181), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL). RESULTS: Using the best cut-off derived from the Youden Index, plasma Aß42/40 yielded an area under the receiver operating characteristic curve (AUC) of 0.949 in distinguishing visually assessed 18F-Florbetaben amyloid PET positivity. The plasma Aß42/40 had a significantly superior AUC than p-tau181, GFAP, and NfL in the 167 participants with measurements for all four biomarkers. Next, we analyzed 99 participants, including only the HC and those with MCI, and discovered that plasma Aß42/40 outperformed the other plasma biomarkers, suggesting its ability to detect early amyloid accumulation. Using the Centiloid scale (CL), Spearman's rank correlation coefficient between plasma Aß42/40 and CL was -0.767. Among the 15 participants falling within the CL values indicative of potential future amyloid accumulation (CL between 13.5 and 35.7), plasma Aß42/40 categorized 61.5% (8/13) as Aß-positive, whereas visual assessment of amyloid PET identified 20% (3/15) as positive. CONCLUSION: Plasma Aß42/40 measured using the fully automated HISCL platform showed excellent performance in identifying Aß accumulation in the brain in a well-characterized cohort. This equipment may be useful for screening amyloid pathology because it has the potential to detect early amyloid pathology and is readily applied in clinical settings.

Machine learning molecular dynamics simulation of CO-driven formation of Cu clusters on the Cu(111) surface.

The behavior of adsorbate-induced surface transformation can be clearly understood given the mechanical aspects of such phenomenon are well described at the atomic level. In this study, we provide the atomic-level description on the formation of Cu clusters on the Cu(111) surface by performing set of molecular dynamics simulations driven by machine-learning force-field. The simulations at 450 K-550 K show clusters are formed within a hundred of ns when the Cu surface is exposed with CO. On the other hand, no cluster is formed within the same time interval on the clean Cu surface even at 550 K, which signifies the importance of CO exposure to the surface transformation. The effect of temperature to the formation of clusters is also investigated. The CO-decorated Cu clusters ranging from dimer to hexamer are detected within a hundred of ns at 450 K. Lowering the temperature to 350 K does not result in the formation of clusters within a hundred ns due to the scarce detachments of adatom, while raising the temperature to 550 K results in the formation of more clusters, ranging from dimer to heptamer, but with shorter lifetimes. The clusters can be formed directly through instantaneous detachment of a group of step-atoms, or indirectly by aggregation of wandering Cu monomers and smaller clusters on the surface terrace. The preference to the indirect mechanism is indicated by the higher frequency of its occurrence. Set of nudged elastic band calculations has been performed to confirm the promotion of CO adsorptions to the detachment of Cu step-atoms by lowering the detachment barrier.

[Molecular Mechanisms of Pituitary Tumorigenesis].

Scientific advances have improved our understanding of the molecular pathological mechanisms underlying pituitary tumorigenesis, allowing us to analyze tumors in a more precise manner and to identify the tumors that have a greater risk of aggressive behavior at an earlier stage. Based on these molecular pathological findings, the classification of pituitary tumors has been revised over the last two decades to better describe their biological and clinical behavior and to identify prognostic markers of aggressiveness and poor prognosis. Understanding pituitary tumors at the molecular level has enabled increasingly targeted treatments with safety and efficacy validated in randomized trials. This paper reviews recent advances in the study of pituitary tumors, particularly pituitary endocrine tumors, and craniopharyngiomas, and describes potential therapies for pituitary tumors.

Volumetric measurement of paranasal sinuses and its clinical significance in pituitary neuroendocrine tumors operated using an endoscopic endonasal approach.

Objective: Endoscopic endonasal surgery (EES) for deep intracranial lesions has gained popularity following recent developments in endoscopic technology. The operability of invasive pituitary neuroendocrine tumors (PitNETs) depends on the anatomy of the nasal cavity and paranasal sinus. This study aimed to establish a simple volume reconstruction algorithm of the nasal cavity and paranasal sinus. Additionally, this is the first study to demonstrate the relationship between the segmentation method and the clinical significance in patients with PitNET. Methods: Pre-and postoperative tumor volumes were analyzed in 106 patients with primary (new-onset) PitNETs (80 nonfunctioning and 26 functioning) who underwent EES. The efficiency and accuracy of the semiautomatic segmentation with manual adjustments (SSMA) method was compared with other established segmentation methods for volumetric analysis in the nasal cavity and paranasal sinuses. Correlations between the measured nasal cavity and paranasal sinus volumes and the extent of tumor removal were evaluated. Results: The SSMA method yielded accurate and time-saving results following the volumetric analyses of nasal cavity and paranasal sinuses with complex structures. Alternatively, the manual and semiautomatic segmentation methods proved time-consuming and inaccurate, respectively. The sphenoid sinus volume measured by SSMA was significantly correlated with the extent of tumor removal in patients with nonfunctioning Knosp grade 3 and 4 PitNET (r = 0.318; p = 0.015). Conclusion: The volume of sphenoid sinus potentially could predict the extent of resection due to better visualization of the tumor for PitNETs with CS invasion.

A simple combined approach using anterior transpetrosal and retrosigmoid approach: A case report.

Background: A combined transpetrosal approach (CTP) is often used for large lesions in the posterior cranial fossa (PCF). Although CTP provides a wide surgical corridor, it has complex and time-consuming bony work of mastoidectomy and cosmetic issues. Here, we describe a simple combined surgical technique to approach the supratentorial region, anterolateral surface of the brainstem, petroclival region, and foramen magnum by drilling only the petrous apex with a combination of retrosigmoid approach (RA). Clinical presentation: A 27-year-old female was referred with extra-axial left cerebellopontine angle space-occupying epidermoid cyst extending to the prepontine cistern, anterior to the basilar artery, superior to the chiasma, and caudally to the foramen magnum. A one-stage surgical procedure using the anterior transpetrosal approach (ATP) and RA was performed after one-piece temporal-suboccipital craniotomy. These two approaches complemented each other well. Near-total removal was achieved. Conclusion: A one-stage surgical procedure using ATP and RA provides the wider viewing and better visualization of the PCF with minimal technical difficulty.

Diagnostic Value of the Vesical Imaging-Reporting and Data System in Bladder Urothelial Carcinoma with Variant Histology.

The value of the Vesicle Imaging-Reporting and Data System (VI-RADS) in the diagnosis of muscle-invasive bladder cancer (MIBC) for urothelial carcinoma with variant histology (VUC) remains unknown. We retrospectively evaluated 360 consecutive patients with bladder cancer (255 pure urothelial carcinoma [PUC] and 69 VUC) who underwent multiparametric magnetic resonance imaging between 2011 and 2019. VI-RADS scores assigned by four readers were significantly higher for the VUC group than for the PUC group (p < 0.05). In the cohort of 122 pair-matched patients, there was no significant difference in VI-RADS score distribution between the PUC and VUC groups for all readers (p > 0.05). The area under the receiver operating characteristic curve for MIBC diagnosis via overall VI-RADS score was 0.93-0.94 for PUC and 0.89-0.92 for VUC, with no significant difference between the PUC and VUC groups (p = 0.32-0.60). These data suggests that VI-RADS scores achieved high diagnostic performance for detection of muscle invasion in both PUC and VUC. PATIENT SUMMARY: The Vesical Imaging-Reporting and Data System (VI-RADS) is a standardized system for reporting on detection of muscle-invasive bladder cancer via magnetic resonance imaging (MRI) scans. Our study shows that VI-RADS is also highly accurate for diagnosis for different variants of muscle-invasive bladder cancer, with good inter-reader agreement.

Impact of Amyloid and Tau PET on Changes in Diagnosis and Patient Management.

BACKGROUND AND OBJECTIVES: Previous studies have evaluated the diagnostic effect of amyloid PET in selected research cohorts. However, these studies did not assess the clinical impact of the combination of amyloid and tau PETs. Our objective was to evaluate the association of the combination of 2 PETs with changes in diagnosis, treatment, and management in a memory clinic cohort. METHODS: All participants underwent amyloid [18F]florbetaben PET and tau PET using [18F]PI-2620 or [18F]Florzolotau, which are potentially useful for the diagnosis of non-Alzheimer disease (AD) tauopathies. Dementia specialists determined a pre- and post-PET diagnosis that existed in both a clinical syndrome (cognitive normal [CN], mild cognitive impairment [MCI], and dementia) and suspected etiology, with a confidence level. In addition, the dementia specialists determined patient treatment in terms of ancillary investigations and management. RESULTS: Among 126 registered participants, 84.9% completed the study procedures and were included in the analysis (CN [n = 40], MCI [n = 25], AD [n = 20], and non-AD dementia [n = 22]). The etiologic diagnosis changed in 25.0% in the CN, 68.0% in the MCI, and 23.8% with dementia. Overall changes in management between pre- and post-PET occurred in 5.0% of CN, 52.0% of MCI, and 38.1% of dementia. Logistic regression analysis revealed that tau PET has stronger associations with change management than amyloid PET in all participants and dementia groups. DISCUSSION: The combination of amyloid and tau PETs was associated with changes in management and diagnosis of MCI and dementia, and the second-generation tau PET has a strong impact on the changes in diagnosis and management in memory clinics. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that the combination of amyloid and tau PETs was associated with changes in management and diagnosis of MCI and dementia.

Intergenerational concordance of brain structure between depressed mothers and their never-depressed daughters.

AIM: Parents have significant genetic and environmental influences, which are known as intergenerational effects, on the cognition, behavior, and brain of their offspring. These intergenerational effects are observed in patients with mood disorders, with a particularly strong association of depression between mothers and daughters. The main purpose of our study was to investigate female-specific intergenerational transmission patterns in the human brain among patients with depression and their never-depressed offspring. METHODS: We recruited 78 participants from 34 families, which included remitted parents with a history of depression and their never-depressed biological offspring. We used source-based and surface-based morphometry analyses of magnetic resonance imaging data to examine the degree of associations in brain structure between four types of parent-offspring dyads (i.e. mother-daughter, mother-son, father-daughter, and father-son). RESULTS: Using independent component analysis, we found a significant positive correlation of gray matter structure between exclusively the mother-daughter dyads within brain regions located in the default mode and central executive networks, such as the bilateral anterior cingulate cortex, posterior cingulate cortex, precuneus, middle frontal gyrus, middle temporal gyrus, superior parietal lobule, and left angular gyrus. These similar observations were not identified in other three parent-offspring dyads. CONCLUSIONS: The current study provides biological evidence for greater vulnerability of daughters, but not sons, in developing depression whose mothers have a history of depression. Our findings extend our knowledge on the pathophysiology of major psychiatric conditions that show sex biases and may contribute to the development of novel interventions targeting high-risk individuals.

Findings of 18 F-PI-2620 tau PET imaging in patients with Alzheimer's disease and healthy controls in relation to the plasma P-tau181 levels in a Japanese sample.

BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia worldwide. In AD, abnormal tau accumulates within neurons of the brain, facilitated by extracellular ß-amyloid deposition, leading to neurodegeneration, and eventually, cognitive impairment. As this process is thought to be irreversible, early identification of abnormal tau in the brain is crucial for the development of new therapeutic interventions. AIMS: 18 F-PI-2620 is one of the second-generation tau PET tracers with presumably less off-target binding than its predecessors. Although a few clinical studies have recently reported the use of 18 F-PI-2620 tau PET in patients with AD, its applicability to AD is yet to be thoroughly examined. METHODS: In the present pilot study, we performed 18 F-PI-2620 tau PET in seven cases of probable AD (AD group) and seven healthy controls (HC group). Standardized uptake value ratios (SUVR) in regions of interest (ROIs) in the medial temporal region and neocortex were compared between the AD and HC groups. Furthermore, correlations between regional SUVR and plasma p-tau181 as well as cognitive test scores were also analyzed. RESULTS: The uptake of 18 F-PI-2620 was distinctly increased in the AD group across all the ROIs. SUVR in all the target ROIs were significantly correlated with plasma p-tau181 levels, as well as with MMSE and ADAS-cog scores. DISCUSSION & CONCLUSION: Our results add to accumulating evidence suggesting that 18 F-PI-2620 is a promising tau PET tracer that allows patients with AD to be distinguished from healthy controls, although a study with a larger sample size is warranted.

Endoscopic Endonasal Reconstruction Using a Pedicled Middle Turbinate Flap for Spontaneous Cerebrospinal Fluid Rhinorrhea.

ABSTRACT: Although endoscopic skull-base reconstruction protocols to reduce cerebrospinal fluid (CSF) leakage are reported, the most effective management strategies have not been determined. We describe the successful repair of a spontaneous CSF leak using a vascularized middle turbinate flap (MTF) via an endonasal endoscopic approach and also discuss the effective reconstruction with other available pedicled flaps. An 11-year-old girl had a 5-month history of intermittent CSF rhinorrhea. Endoscopic endonasal skull base reconstruction was performed using the pedicled MTF technique, which sufficiently covered the unilateral cribriform plate and ethmoidal fovea including suspicious leakage site. Middle turbinate flaps may be good for repairing spontaneous CSF leaks, which commonly have small, low-flow CSF fistulas around a cribriform plate. As spontaneous CSF leaks are known to have a higher recurrence rate, MTF may be advantageous because more of the normal structures are retained.

Long-Term Outcomes of Endoscopic Cyst Fenestration for Rathke Cleft Cyst.

OBJECTIVE: We sought to elucidate the long-term surgical outcomes and incidence of recurrence and reoperation of endoscopic endonasal cyst fenestration for Rathke cleft cyst (RCC). METHODS: A retrospective review of the chart and operation record of RCC surgical cases between January 2008 and August 2021 at our institution was conducted. Patient characteristics, intraoperative findings, and postoperative follow-up outcomes were evaluated. RESULTS: A total of 27 patients were analyzed, with a median postoperative follow-up period of 52 months (range, 1-150 months). Preoperative symptoms were visual dysfunction (59%), headache (41%), and pituitary dysfunction (22%). Endoscopic cyst fenestration was performed in all patients. Ten (37%) patients had intraoperative cerebrospinal fluid leakage. Among them, the only patient in whom sellar floor reconstruction was not performed experienced a repair operation due to postoperative cerebrospinal fluid leakage. No patients experienced postoperative hypopituitarism. Preoperative headache, visual dysfunction, and pituitary hormone disorder improved in 73%, 75%, and 67% of patients, respectively. Although postoperative cyst regrowth was observed in 8 patients (30%), no patient experienced worsening or novel symptoms and none required reoperation. CONCLUSIONS: Patients with a symptomatic RCC can be effectively treated with endoscopic endonasal cyst fenestration. Reversal of the presenting symptoms resulted, including headache, visual dysfunction, and pituitary hormone dysfunction, in the majority of patients. In our series, appropriate reconstruction of the sellar floor reduced the risk of postoperative cerebrospinal fluid leakage without impacting cyst regrowth. This simple technique appears to effectively disrupt cyst progression in most cases, even after a relatively long-term follow-up period.

Clinical utility of the Bosniak classification version 2019: Diagnostic value of adding magnetic resonance imaging to computed tomography examination.

PURPOSE: To assess the impact of the updated Bosniak classification (BC2019) for cystic renal masses (CRMs) on interobserver agreement between radiologists and urologists and the diagnostic value of adding MRI to CT examination (combined CT/MRI). METHOD: This study included 103 CRMs from 83 consecutive patients assessed using contrast-enhanced CT and MRI between 2010 and 2016. Nine readers in three groups (three radiologists, three radiology residents, and three urologists) reviewed CT alone and the combined CT/MRI using BC2019. Bosniak category was determined by consensus in each group for diagnosing malignancy, with a cut-off category of ≧III. Interobserver agreement was assessed using Fleiss' kappa values. The effect of CT or combined CT/MRI on the diagnosis of malignancy was assessed using McNemar's test. RESULTS: Interobserver agreement of BC2019 for CT alone was substantial for radiologists and residents, moderate for urologists (0.77, 0.63, and 0.58, respectively). Interobserver agreement of BC2019 for combined CT/MRI was substantial for all three groups (radiologists: 0.78; residents: 0.65; and urologists: 0.61). Among residents, the sensitivity/specificity/accuracy rates of combined CT/MRI vs. CT alone were 82.1/74.7/76.7% vs. 75.0/66.7/68.9%, and specificity and accuracy were significantly higher for combined CT/MRI than that for CT alone (p = 0.03 and 0.008, respectively). Similarly, sensitivity/specificity/accuracy values were significantly higher for combined CT/MRI among urologists (78.6/73.3/74.8% vs. 64.3/64.0/64.1%, p = 0.04/0.04/0.008). However, sensitivity/specificity/accuracy did not significantly differ between the two among radiologists (89.3/74.7/78.6% vs. 85.7/73.3/76.7%, p = 0.32/0.56/0.32). CONCLUSIONS: Combined CT/MRI is useful for diagnosing malignancy in patients with CRMs using BC2019, especially for non-expert readers.

White matter alterations in the dorsal attention network contribute to a high risk of unsafe driving in healthy older people.

Aim: Healthy older drivers may be at high risk of fatal traffic accidents. Our recent study showed that volumetric alterations in gray matter in the brain regions within the dorsal attention network (DAN) were strongly related to the risk of unsafe driving in healthy older people. However, the relationship between white matter (WM) structural connectivity and driving ability in healthy older people is still unclear. Methods: We used diffusion tensor imaging to examine the association between microstructural alterations in the DAN and the risk of unsafe driving among healthy older people. We enrolled 32 healthy older individuals aged over 65 years and screened unsafe drivers using an on-road driving test. We then determined the pattern of WM aberrations in unsafe drivers using tract-based spatial statistics. Results: The analysis demonstrated that unsafe drivers had significantly higher axial diffusivity values in nine WM clusters compared with safe drivers. These results were primarily observed bilaterally in the dorsal superior longitudinal fasciculus, which is involved in the DAN. Furthermore, correlation analyses showed that higher axial diffusivity values in the superior longitudinal fasciculus were associated with lower Trail Making Test A scores within unsafe drivers. This result suggests that functionally, WM microstructural alterations in the DAN are associated with attention problems, which may contribute to the risk of unsafe driving among healthy older people. Conclusion: Our findings may elucidate the neurobiological mechanisms underlying the increased risk of unsafe driving in healthy older people, potentially facilitating the development of new interventions to prevent fatal accidents.

Evaluation of [18F]PI-2620, a second-generation selective tau tracer, for assessing four-repeat tauopathies.

Tau aggregates represent a key pathologic feature of Alzheimer's disease and other neurodegenerative diseases. Recently, PET probes have been developed for in vivo detection of tau accumulation; however, they are limited because of off-target binding and a reduced ability to detect tau in non-Alzheimer's disease tauopathies. The novel tau PET tracer, [18F]PI-2620, has a high binding affinity and specificity for aggregated tau; therefore, it was hypothesized to have desirable properties for the visualization of tau accumulation in Alzheimer's disease and non-Alzheimer's disease tauopathies. To assess the ability of [18F]PI-2620 to detect regional tau burden in non-Alzheimer's disease tauopathies compared with Alzheimer's disease, patients with progressive supranuclear palsy (n = 3), corticobasal syndrome (n = 2), corticobasal degeneration (n = 1) or Alzheimer's disease (n = 8), and healthy controls (n = 7) were recruited. All participants underwent MRI, amyloid ß assessment and [18F]PI-2620 PET (Image acquisition at 60-90 min post-injection). Cortical and subcortical tau accumulations were assessed by calculating standardized uptake value ratios using [18F]PI-2620 PET. For pathologic validation, tau pathology was assessed using tau immunohistochemistry and compared with [18F]PI-2620 retention in an autopsied case of corticobasal degeneration. In Alzheimer's disease, focal retention of [18F]PI-2620 was evident in the temporal and parietal lobes, precuneus, and cingulate cortex. Standardized uptake value ratio analyses revealed that patients with non-Alzheimer's disease tauopathies had elevated [18F]PI-2620 uptake only in the globus pallidus, as compared to patients with Alzheimer's disease, but not healthy controls. A head-to-head comparison of [18F]PI-2620 and [18F]PM-PBB3, another tau PET probe for possibly visualizing the four-repeat tau pathogenesis in non-Alzheimer's disease, revealed different retention patterns in one subject with progressive supranuclear palsy. Imaging-pathology correlation analysis of the autopsied patient with corticobasal degeneration revealed no significant correlation between [18F]PI-2620 retention in vivo. High [18F]PI-2620 uptake at 60-90 min post-injection in the globus pallidus may be a sign of neurodegeneration in four-repeat tauopathy, but not necessarily practical for diagnosis of non-Alzheimer's disease tauopathies. Collectively, this tracer is a promising tool to detect Alzheimer's disease-tau aggregation. However, late acquisition PET images of [18F]PI-2620 may have limited utility for reliable detection of four-repeat tauopathy because of lack of correlation between post-mortem tau pathology and different retention pattern than the non-Alzheimer's disease-detectable tau radiotracer, [18F]PM-PBB3. A recent study reported that [18F]PI-2620 tracer kinetics curves in four-repeat tauopathies peak earlier (within 30 min) than Alzheimer's disease; therefore, further studies are needed to determine appropriate PET acquisition times that depend on the respective interest regions and diseases.