Total Volume Research Articles

Updated automated PROMISE assessment: Treatment response evaluation based on PSMA PET/CT.

48 Background: PSMA PETs can track treatment response in patients with prostate cancer. Recent integration of the RECIP framework with PROMISE v2 allows quantitative assessment of PSMA PETs. While useful for assessing differentially responding lesions, manual measurement and tracking is cumbersome and PSA reliance can be misleading. We evaluated an automated AI-enabled platform, aPROMISE, for longitudinal lesion tracking to evaluate treatment response based solely upon tumor volume. Methods: Patients with castration sensitive or resistant disease undergoing 18F-DCFPyL PET/CTs during workup and at ≥3 months after treatment were included. Tracer-avid lesions were identified using the aPROMISE algorithm. Detected lesions were manually approved by an experienced nuclear medicine physician. After lesion identification and approval, the total tumor volume was calculated. The corresponding low-dose CT was auto-segmented, allowing anatomic compartment (prostate/bed, node, bone, or visceral) annotation of 18F-DCFPyL-avid lesions. Baseline and follow-up PETs were deformably co-registered to automatically match individual lesions if they were in the same anatomic compartment, and had overlap <10 mm center-to-center (<50 mm for rib lesions). Unmatched lesions on follow-up PET were noted as new. Response was assessed as CR (no avidity in follow-up), PR (volume decrease ≥30% without new lesions), SD (volume decrease ≥30% with new lesions), or PD (volume increase ≥20% plus new lesions). Volume changes at the total tumor and individual lesion levels were also assessed independent of RECIP imaging criteria. Results: The automated algorithm assigned the correct RECIP classification in 97% of the 67 cases with 14 as CR, 14 as PR, 20 as SD, and 19 as PD. 1027 of the 1686 lesions identified on baseline PET were seen on follow-up. 673 of the 1700 lesions identified on follow-up PET were new. Conclusions: For response assessment using 18F-DCFPyL PET/CT and RECIP imaging criteria, the automated algorithm and manual detection achieved the same clinical classifications. Automated approaches may allow more granular lesion analysis The precision and accuracy this automated process is being validated in prospective clinical studies.

Association between PET-based TheraP eligibility and 177Lu-PSMA-617 (LuPSMA) outcomes in VISION-eligible patients with metastatic castration-resistant prostate cancer (mCRPC).

41 Background: The optimal threshold based on pre-treatment PET for patient selection for LuPSMA is yet to be defined. TheraP trial applied a high threshold for PSMA-expression on PSMA PET and utilized FDG PET to exclude FDG-avid/non-PSMA-avid disease while the VISION trial used only PSMA PET with a lower threshold of PSMA-expression. The stricter criteria in TheraP trial doubled the screening failure rate compared to VISION trial, 28% vs. 12.6%. In this study among VISION-eligible patients, we aimed to compare the outcome of those who were TheraP-Eligible (TheraP-E) to TheraP-Ineligible (TheraP-I). Further, the prognostic value of FDG-PET phenotyping is investigated. Methods: This retrospective cohort study evaluated consecutive VISION-eligible mCRPC patients who received at least one cycle of LuPSMA and had both PSMA- and FDG-PET within one month of each other between June 2022 and January 2023. Patients were blindly classified as TheraP-E vs. TheraP-I. We compared whole-body semiquantitative parameters including total tumor volume (TTV), SUVmean and SUVmax and outcomes including PSA decline of ≥50% relative to baseline (PSA50), PSA-progression-free survival (PSA-PFS), and overall survival (OS) between the groups. Separately, the patients were dichotomized to having dominant FDG-avid disease (uptake > liver in most sites of disease) vs. non-FDG-avid disease and OS were compared by Cox-regression. Results: 46 patients (median age: 72, ECOG 0-2: 89%, visceral disease: 28%) were included with a median follow-up of 10 months (IQR: 8-14). 14/46 (30%) patients assessed as TheraP-I and had lower PSMA-PET SUVmean and SUVmax compared to TheraP-E patients (5.6 vs. 8.8 and 23 vs. 53, p < 0.001 for both) while other PET parameters including PSMA TTV and FDG parameters (SUVmax, SUVmean and TTV) were not statistically different. TheraP-I patients had lower PSA50 response (21% vs. 56%, p = 0.029) but PSA-PFS and OS were not significantly different compared to TheraP-E patients (Table). 37/46 (80%) patients assessed as FDG-avid had an increased risk of death compared to non-FDG-avid counterparts (Table). Conclusions: In a VISION-eligible population receiving LuPSMA, TheraP imaging-based ineligibility was associated with worse PSA response but with no significant difference in PSA-PFS or OS. Clinical investigation of the more permissive VISION inclusion criteria and the importance of FDG-avid disease using a larger sample size is warranted. [Table: see text]

Effect of Therapeutic Radiation on Polycaprolactone/Hydroxyapatite Biomaterials in a Calvarial Model.

Bone defects caused by cancer resection often require postoperative radiotherapy. Although various synthetic polymers have been introduced as graft materials, their biological behavior after radiation exposure remains unclear. Here, we investigated how polycaprolactone/hydroxyapatite (PCL/HA) implants respond to therapeutic radiation exposure (in terms of volume and bone regeneration). Four 8mm diameter calvaria defects were surgically created on the parietal bone of 6 rabbits. PCL/HA implants made of porous, solid, and hybrid polymers were grafted by random placement in each defect. The fourth defect was left untreated. Four weeks after surgery, radiation exposure was conducted weekly for 6 weeks (total: 48Gy). Micro-computed tomography and histologic analysis were performed at 3 and 6 months, and 6 months postradiation, respectively. The total augmented volumes of all implants showed no significant differences between 3- and 6-months postradiation computed tomography images. In histologic analysis, new bone areas were 0.45±0.11mm2, 2.02±0.34mm2, and 3.60±0.77mm2 in solid, hybrid, and porous polymer grafts, respectively. Bone regeneration was limited to the periphery of the defect in the hybrid and porous polymer grafts, whereas new bone formed inside the porous implant. The total augmented volume of the defect was maintained without significant absorption even after radiation exposure. The PCL/HA implant maintained its structure despite radiation exposure. The porous PCL/HA implant demonstrated excellent bone regeneration, followed by the hybrid and solid implants. The PCL/HA implant is a promising candidate for bone defect reconstruction.

Total and anatomically contextualized quantitative 18F-DCFPyL PET at biochemical recurrence to predict subsequent biochemical progression-free survival in patients with prostate cancer.

33 Background: PSMA PET has been shown to detect more metastasis and alter management at biochemical recurrence (BCR), but it remains to be determined that it changes oncologic outcome. We assessed the quantitative parameters on 18F-DCFPyL PET at BCR and evaluated their association with tumor volume, metastatic locations with the subsequent biochemical progression free survival (bPFS). Methods: This is a retrospective image analysis and longitudinal follow up of a prospective study evaluating 18F-DCFPyL PET in BCR. Patients were treated with androgen deprivation therapy (ADT) and/or metastatic directed therapy (MDT) based on imaging findings. The 18F-DCFPyL PET images were quantitatively analyzed by the aPROMISE application, a semi-automated software for comprehensive analysis and structured reporting of PSMA PET/CT. aPROMISE uses deep learning to segment detailed anatomical information from the CT images and uses this information in combination with the PET image to detect and quantify candidates for prostate cancer lesions. The reader works in tandem with the software to vet the final list of lesions, from which the quantitative assessments and final report is created automatically. Based on the Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE) criteria. SUV mean, PSMA positive total tumor volume (PSMAttv) and aPSMA scores, a quantitative score for tumor burden measuring the interaction of tumor volume and uptake stratified by local tumors (aPSMA-miT), regional lymph nodes (aPSMA-miN) and distant metastases (aPSMA-miMa for extrapelvic metastases, miMb for bone metastases and miMc for other organ metastases) were obtained based on the miTNM classification. The association of these quantitative parameters with the subsequent bPFS was evaluated. Results: 143 patients (age 70.5 ± 7.9, range 50 -93 years; median PSA 2.8, range 0.12 – 1125.9 ng/mL) were included in the quantitative image analysis. 80 of 143 patients (56%) had nodal metastases 51/143 patients (36%) had bone metastases, only 16 of 143 patients (11%) had visceral metastases. With median follow up of 40 months, 82 of 143 patients (57%) have progressed again biochemically after MDT. The median bPFS was 26.9 months. Quantitative analysis of 18F-DCFPyL PET found that the subsequent bPFS is significantly associated with aPSMA-miMb ( P = 0.003), aPSMA-miN ( P = 0.005), aPSMA-miT ( P < 0.001), and PSMAttv ( P = 0.006), but not with SUVmean, SUVmax or aPSMA-miMc. Conclusions: Quantitative image analysis of 18F-DCFPyL PET at BCR may be useful in predicting the subsequent bPFS. Given many patients were treated with MDT and/or ADT, clinical implication of the findings remains to be elucidated to guide treatment intensification based on findings on 18F-DCFPyL PET.

Abstract WP118: Ischemic Core Volumes and Collateral Status Have Diurnal Fluctuations - A Retrospective Cohort Study of 18137 Patients Using Automated Perfusion Imaging

Introduction: Circadian rhythms have recently been shown to influence stroke incidence and progression of infarct. We aimed to describe the diurnal variations in the incidence and perfusion profiles of patients with ischemic stroke using a large, multi-center, automated imaging database. Methods: The RAPID Insights database was queried from 02/01/2016 to 01/31/2022 for patients with perfusion imaging and automated detection of an ischemic stroke due to a presumed large vessel occlusion. Exclusion criteria included: patient age ≤25, mismatch volume of <0 cc, and failure to register a positive value on either cerebral blood flow (CBF) reduction of 38% less than normal or total mismatch volume. Imaging time was subdivided into three epochs: Night: 23:00h-06:59h and Day: 07:00h-14:59h, and Evening: 15:00h-22:59h. Perfusion parameters were defined as the following: core volume was defined as CBF of <30% of normal, penumbra was defined as a Tmax delay of >6 seconds minus core volume, and collateral circulation was estimated with the Hypoperfusion Intensity Ratio (HIR = [Tmax>10s]/[Tmax>6s]), where a higher HIR suggests poorer collateral status. All perfusion parameters were analyzed on a 24-hour continuous cycle. Statistical significance was tested using a sinusoidal regression analysis. Results: A total of 18,137 cases were analyzed. The peak incidence of ischemic stroke occurred around noon. A sinusoidal pattern was present, with larger ischemic core volumes and higher HIR during the night compared to the day: peak ischemic core volume of 23.40 cc occurred with imaging performed at 3:56 AM (p<0.001) and peak HIR of 0.35 at 3:40 AM (p<0.001). Conclusion: We found that ischemic core volumes were larger and collateral status worse at nighttime compared to daytime in this large national database. These findings support the notion that poor collateral recruitment with subsequent larger ischemic stroke volumes may occur at night. Fig 1. Logarithmic values of ischemic core volumes and hypoperfusion intensity ratios (HIR) are plotted against a 24-hour cycle, demonstrating a sinusoidal pattern for both.

The Prognostic Role of Volumetric MRI Evaluation in the Surgical Treatment of Glioblastoma

Background: Glioblastoma is the most common primary brain neoplasm in adults, with a poor prognosis despite a constant effort to improve patient survival. Some neuroradiological volumetric parameters seem to play a predictive role in overall survival (OS) and progression-free survival (PFS). The aim of this study was to analyze the impact of the volumetric areas of contrast-enhancing tumors and perineoplastic edema on the survival of patients treated for glioblastoma. Methods: A series of 87 patients who underwent surgery was retrospectively analyzed; OS and PFS were considered the end points of the study. For each patient, a multidisciplinary revision was conducted in collaboration with the Neuroradiology and Neuro-Oncology Board. Manual and semiautomatic measurements were adopted to perform the radiological evaluation, and the following quantitative parameters were retrospectively analyzed: contrast enhancement preoperative tumor volume (CE-PTV), contrast enhancement postoperative tumor volume (CE-RTV), edema/infiltration preoperative volume (T2/FLAIR-PV), edema/infiltration postoperative volume (T2/FLAIR-RV), necrosis volume inside the tumor (NV), and total tumor volume including necrosis (TV). Results: The median OS value was 9 months, and the median PFS value was 4 months; the mean values were 12.3 and 6.9 months, respectively. Multivariate analysis showed that the OS-related factors were adjuvant chemoradiotherapy (p < 0.0001), CE-PTV < 15 cm3 (p = 0.03), surgical resection > 95% (p = 0.004), and the presence of a “pseudocapsulated” radiological morphology (p = 0.04). Conclusions: Maximal safe resection is one of the most relevant predictive factors for patient survival. Semiautomatic preoperative MRI evaluation could play a key role in prognostically categorizing these tumors.

A Comparison of State-Specific Pediatric Emergency Medical Facility Recognition Programs, 2020.

Prior research suggests that the presence of state-specific pediatric emergency medical facility recognition programs (PFRPs) is associated with high emergency department (ED) pediatric readiness. The PFRPs aim to improve the quality of pediatric emergency care, but individual state programs differ. We aimed to describe the variation in PFRP characteristics and verification requirements and to describe the availability of pediatric emergency care coordinators (PECCs) in states with PFRPs. In mid-2020, we collected information about each PFRP from 3 sources: the state Emergency Medical Services for Children (EMSC) website, the EMSC Innovation and Improvement Center website, or via communication with the state's EMSC program manager. For each state with a PFRP, we documented program characteristics, including program start date, number of tiers, whether participation was required/optional, and requirements for verification. Overall, we identified 17 states with active PFRPs. Five states had only 1 tier or level of recognition whereas the others had multiple. All programs did require presence of a PECC for verification. However, some PRFPs with multiple verification tiers did not require presence of a PECC to achieve each level of verification. In states with PFRPs, EDs with higher total visit volumes, a separate pediatric ED area, located in the Northeast, and earlier program start date were all more likely to have a PECC. There is variation in state PFRPs, although all prioritize the presence of a PECC. We encourage further research on the effect of different aspects of PFRPs on patient outcomes.

Utility of PSMA PET/CT for imaging ductal carcinoma of the prostate.

49 Background: Ductal carcinoma (DC) is the second most commonly encountered histologic variant of prostate cancer. Previous studies have described its molecular features and aggressive behavior, but few have explored the performance of PSMA PET/CT in the initial staging and follow-up of DC. Methods: To address this gap, we performed a single-institution retrospective analysis using the Mayo Clinic PSMA PET database. All patients receiving a PSMA PET/CT scan in the interval of January 1, 2021, to December 31, 2022, were eligible for inclusion. Cases were filtered and categorized by histology at the time of diagnosis to select for pure DAC and mixed ductal variants. Trained research personnel annotated disease- and treatment-related variables. A board-certified radiologist performed tumor burden segmentation with calculations of SUV max, total lesion SUV mean and volume, and total lesion uptake, and ascribed a miPSMA expression score. Results: We queried 1792 patients from our PSMA PET/CT registry and identified 32 (1.8%) patients with a pathologically confirmed DC, including 8 (25%) patients with pure ductal and 25 (75%) patients with mixed histology. The indication for PSMA PET/CT was biochemical progression or restaging for 29 (91%) patients and initial staging for 3 (9%) patients. The median (IQR) time from prostate cancer diagnosis to PSMA PET scan was 41.6 (11.5-64.7) months, during this time 50% (n= 16) of patients developed CRPC. At the time of the PSMA PET/CT scan, the median age was 70 years, the median (IQR) PSA was 0.5 ng/mL (0.2-2.6). The distribution of metastatic spread and quantitative imaging parameters from PSMA PET are shown in the Table. Conclusions: Despite low PSA at the time of imaging, PSMA PET/CT frequently detected high volume osseous and/or visceral metastases in patients with DC. However, it is noteworthy that more than 50% of patients with DC had a low miPSMA score (0-1). Additional studies are needed to better understand the performance of novel imaging modalities when evaluating variant prostate cancers. [Table: see text]

"Non-Eloquent" brain regions predict neuropsychological outcome in tumor patients undergoing awake craniotomy.

Supratotal resection of primary brain tumors is being advocated especially when involving "non-eloquent" tissue. However, there is extensive neuropsychological data implicating functions critical to higher cognition in areas considered "non-eloquent" by most surgeons. The goal of the study was to determine pre-surgical brain regions that would be predictive of cognitive outcome at 4-6 months post-surgery. Cortical reconstruction and volumetric segmentation were performed with the FreeSurfer-v6.0 image analysis suite. Linear regression models were used to regress cortical volumes from both hemispheres, against the total cognitive z-score to determine the relationship between brain structure and broad cognitive functioning while controlling for age, sex, and total segmented brain volume. We identified 62 consecutive patients who underwent planned awake resections of primary (n = 55, 88%) and metastatic at the University of New Mexico Hospital between 2015 and 2019. Of those, 42 (23 males, 25 left hemispheric lesions) had complete pre and post-op neuropsychological data available and were included in this study. Overall, total neuropsychological functioning was somewhat worse (p = 0.09) at post-operative neuropsychological outcome (Mean = -.20) than at baseline (Mean = .00). Patients with radiation following resection (n = 32) performed marginally worse (p = .036). We found that several discrete brain volumes obtained pre-surgery predicted neuropsychological outcome post-resection. For the total sample, these volumes included: left fusiform, right lateral orbital frontal, right post central, and right paracentral regions. Regardless of lesion lateralization, volumes within the right frontal lobe, and specifically right orbitofrontal cortex, predicted neuropsychological difference scores. The current study highlights the gaps in our current understanding of brain eloquence. We hypothesize that the volume of tissue within the right lateral orbital frontal lobe represents important cognitive reserve capacity in patients undergoing tumor surgery. Our data also cautions the neurosurgeon when considering supratotal resections of tumors that do not extend into areas considered "non-eloquent" by current standards.

Comparison of brain imaging and physical health between research and clinical neuroimaging cohorts of ageing.

To compare brain MRI measures between Adult Changes in Thought (ACT) participants who underwent research, clinical, or both MRI scans, and clinical health measures across the groups and non-MRI subjects. Retrospective cohort study leveraging MRI, clinical, demographic, and medication data from ACT. Three neuroradiologists reviewed MRI scans using NIH Neuroimaging Common Data Elements (CDEs). Total brain and white matter hyperintensity (WMH) volumes, clinical characteristics, and outcome measures of brain and overall health were compared between groups. 1166 MRIs were included (77 research, 1043 clinical, and 46 both) and an additional 3146 participants with no MRI were compared. Compared to the group with research MRI only, the clinical MRI group had higher prevalence of the following: acute infarcts, chronic haematoma, subarachnoid haemorrhage, subdural haemorrhage, haemorrhagic transformation, and hydrocephalus (each P < .001). Quantitative WMH burden was significantly lower (P < .001) and total brain volume significantly higher (P < .001) in research MRI participants compared to other MRI groups. Prevalence of hypertension, self-reported cerebrovascular disease, congestive heart failure, dementia, and recent hospitalization (all P < .001) and diabetes (P = .002) differed significantly across groups, with smaller proportions in the research MRI group. In ageing populations, significant differences were observed in MRI metrics between research MRI and clinical MRI groups, and clinical health metric differences between research MRI, clinical MRI, and no-MRI groups. This questions whether research cohorts can adequately represent the greater ageing population undergoing imaging. These findings may also be useful to radiologists when interpreting neuroimaging of ageing.

Centrilobular emphysema and airway dysanapsis: factors associated with low respiratory function in younger smokers.

Low respiratory function in young adulthood is one of the important factors in the trajectory leading to the future development of COPD, but its morphological characteristics are not well characterised. We retrospectively enrolled 172 subjects aged 40-49 years with ≥10 pack-years smoking history who underwent lung cancer screening by computed tomography (CT) and spirometry at two Japanese hospitals. Emphysema was visually assessed according to the Fleischner Society guidelines and classified into two types: centrilobular emphysema (CLE) and paraseptal emphysema (PSE). Airway dysanapsis was assessed with the airway/lung ratio (ALR), which was calculated by the geometric mean of the lumen diameters of the 14 branching segments divided by the cube root of total lung volume on a CT scan. Among the subjects, CLE and PSE were observed in 20.9% and 30.8%, respectively. The mean ALR was 0.04 and did not differ between those with and without each type of emphysema. Multivariable regression analysis models adjusted for age, sex, body mass index and smoking status indicated that CLE and a low ALR were independently associated with lower forced expiratory volume in 1 s (FEV1)/forced vital capacity (estimate -1.64 (95% CI -2.68- -0.60) and 6.73 (95% CI 4.24-9.24), respectively) and FEV1 % pred (estimate -2.81 (95% CI -5.10- -0.52) and 10.9 (95% CI 5.36-16.4), respectively). CLE and airway dysanapsis on CT were independently associated with low respiratory function in younger smokers.

Response evaluation criteria in PSMA PET/CT (RECIP 1.0) in metastatic castration-resistant prostate cancer.

45 Background: Response Evaluation Criteria in Prostate-Specific Membrane Antigen (PSMA) PET/CT (RECIP 1.0) initially integrated software-based quantitative assessment of PSMA-positive total tumor volume (PSMA-VOL). Clinical implementation of such software is not expected soon, limiting the use of RECIP in practice. This study aimed to assess the agreement of RECIP determined using tumor segmentation software (quantitative RECIP) with RECIP determined by qualitative reads by nuclear medicine physicians (visual RECIP) for response evaluation in metastatic castration-resistant prostate cancer. Methods: This multicenter retrospective study at three academic centers included patients who received lutetium-177 (177Lu) PSMA treatment between December 2014 and July 2019. PSMA PET/CT images at baseline and 12 weeks were assessed qualitatively by five nuclear medicine physicians for changes in PSMA-VOL and for new lesions. Quantitative changes in PSMA-VOL were also measured using tumor segmentation software. The status of new lesions was combined with qualitative changes in PSMA-VOL to determine visual RECIP and with quantitative changes in PSMA-VOL to determine quantitative RECIP. The primary outcomes were the agreement between visual and quantitative RECIP and the interreader reliability of visual RECIP according to the Fleiss κ. The secondary outcome was the association of visual RECIP with overall survival according to Cox regression. Results: A total of 124 patients (median age, 73 years [IQR, 67–76 years]) were included. Forty (32%) and 84 (68%) patients had quantitative RECIP progressive disease (PD) and non-PD, respectively. Agreement between visual versus quantitative RECIP was excellent (κ=0.89; 118 of 124 patients [95%]). Agreement among readers in classifying visual RECIP PD versus non-PD was excellent (κ=0.81; 103 of 124 patients [83%]). RECIP-PD was associated with significantly shorter overall survival compared with RECIP-nonPD (hazard ratio, 2.6 [95%CI: 1.7, 3.8]; P &lt;.001). Conclusions: Qualitatively assessed RECIP demonstrated excellent agreement with quantitative RECIP and excellent interreader reliability, and can be readily implemented in clinical practice for response evaluation in patients with metastatic castration-resistant prostate cancer undergoing 177Lu-PSMA therapy and possible other systemic therapies.

Analysing the impact of comorbid conditions and media coverage on online symptom search data: a novel AI-based approach for COVID-19 tracking

Background Web search data have proven to bea valuable early indicator of COVID-19 outbreaks. However, the influence of co-morbid conditions with similar symptoms and the effect of media coverage on symptom-related searches are often overlooked, leading to potential inaccuracies in COVID-19 simulations. Method This study introduces a machine learning-based approach to estimate the magnitude of the impact of media coverage and comorbid conditions with similar symptoms on online symptom searches, based on two scenarios with quantile levels 10–90 and 25–75. An incremental batch learning RNN-LSTM model was then developed for the COVID-19 simulation in Australia and New Zealand, allowing the model to dynamically simulate different infection rates and transmissibility of SARS-CoV-2 variants. Result The COVID-19 infected person-directed symptom searches were found to account for only a small proportion of the total search volume (on average 33.68% in Australia vs. 36.89% in New Zealand) compared to searches influenced by media coverage and comorbid conditions (on average 44.88% in Australia vs. 50.94% in New Zealand). The proposed method, which incorporates estimated symptom component ratios into the RNN-LSTM embedding model, significantly improved COVID-19 simulation performance. Conclusion Media coverage and comorbid conditions with similar symptoms dominate the total number of online symptom searches, suggesting that direct use of online symptom search data in COVID-19 simulations may overestimate COVID-19 infections. Our approach provides new insights into the accurate estimation of COVID-19 infections using online symptom searches, thereby assisting governments in developing complementary methods for public health surveillance.

Submarine pyroclastic deposits from 7.3 ka caldera-forming Kikai-Akahoya eruption

Extensive submarine pyroclastic deposits were discovered around the Kikai caldera, Southwest Japan, which originated from the caldera-forming Kikai-Akahoya (K-Ah) eruption that occurred at 7.3 ka. This submarine pyroclastic unit originated from a pyroclastic density current (PDC) that entered the sea and was transformed into a subaqueous density current. Our high-resolution marine seismic reflection surveys reveal that the uppermost unit exhibiting prominent seismic facies thins radially away from the caldera and covers >4500 km2 of the seafloor. The estimated volume of the submarine deposits is >71 km3 based on the isopach map. Seismic sequence stratigraphic analyses and correlation of shard glass compositions from the piston core and remotely operated vehicle samples with those from subaerial outcrops identified the unit as pyroclastic deposits produced by the K-Ah eruption. The geomorphological features of the unit indicate a long runout distance (i.e., 40 km), exponential thinning with increasing distance from the source, and a depression-filling nature of the deposits suggesting that the unit was formed predominantly by a density current that entered the water. The quantitative comparisons of geometric shape and its thinning rate, including that for non-volcanic density currents, indicate that the subaerial PDC entering into the water was transported as a dilute density current in the water. We propose that the formation of these dilute density currents transformed by PDCs probably requires sufficient water depth, as inferred also from previous analog experiments. Adding on-land ignimbrite of 5 km3 and widespread tephra of 249–374 km3, our estimate of submarine pyroclastic deposits of >71 km3 leads to a total bulk volume of the K-Ah eruption of 332–457 km3 (133–183 km3 in DRE), making it probably the largest eruption of the Holocene.

Global Distribution and Volume of Cryptomare and Visible Mare on the Moon From Gravity and Dark Halo Craters

AbstractThe present‐day distribution of mare basalts on the Moon is an important constraint on the timing, duration, and flux of volcanism on the Moon. In this work, we find the global distribution of visible mares and cryptomares using the effective density (ρeff) of the Moon, which is sensitive to the vertical density distribution of the crust. We compute ρeff using the Gravity Recovery and Interior Laboratory (GRAIL) data and the Lunar Orbiter Laser Altimeter (LOLA) topography data. We apply this ρeff approach to the search of cryptomare for the first time, and we use a higher resolution grid and larger search area to constrain visible mare thicknesses compared to previous work. We use a Bayesian approach to find the distribution of mare thicknesses and density gradients of the underlying crust that is consistent with the localized ρeff. Assuming a bulk density of the mare basalts of 3,460 kg/m3, we find a mean visible mare thickness of km which is consistent with previous work. We find a candidate cryptomare volume of km3 representing more than half of the total mare volume on Moon. This volume is consistent with the higher end of the previously proposed values. Finally, we search for dark halo craters (DHC) globally to obtain geologic evidence of cryptomares and find 258 craters. Our results are consistent with extensive ancient volcanism, which explains the previously identified discrepancy between the early high volcanic flux predicted by thermal models of the Moon and the dearth of ancient volcanic deposits currently exposed.

Increased plasma lipocalin‐2 levels are associated with nonmotor symptoms and neuroimaging features in patients with Parkinson's disease

AbstractLipocalin‐2 (LCN2) is essential for the regulation of neuroinflammation and cellular uptake of iron. This study aimed to evaluate plasma LCN2 levels and explore their correlation with clinical and neuroimaging features in Parkinson's disease (PD) patients. Enzyme‐linked immunosorbent assay (ELISA) was used to measure plasma LCN2 levels in 120 subjects. Evaluation of motor symptoms and nonmotor symptoms in PD patients was assessed by the associated scales. Voxel‐based morphometry (VBM) was used to evaluate brain volume alterations, and quantitative susceptibility mapping (QSM) was used to quantitatively analyze brain iron deposition in 46 PD patients. Plasma LCN2 levels were significantly higher in PD patients than those in healthy controls. LCN2 levels were negatively correlated with Montreal Cognitive Assessment (MoCA) scores, total brain gray matter volume (GMV), and GMV/total intracranial volume (TIV) ratio, but positively correlated with Hamilton Anxiety Rating Scale (HAMD) scores and mean QSM values of the bilateral substantial nigra (SN). Receiver operating characteristic (ROC) curves confirmed that plasma LCN2 levels had good predictive accuracy for PD. The results suggest that plasma LCN2 levels have potential as a biomarker for the diagnosis of PD. LCN2 may be a therapeutic target for neuroinflammation and brain iron deposition.

Assessing the clinical utility of rapid post-therapy whole-body digital SPECT/CT in evaluating early treatment response of 177Lu-PSMA-617 treatment.

32 Background: Multi-detector cadmium-zinc-telluride (CZT) based whole-body digital SPECT/CT is a new generation of imaging system. We aim to assess the clinical utility of rapid post-therapy whole-body SPECT/CT scan in evaluating early treatment response of 177Lu-PSMA-617 treatment. Methods: We retrospectively reviewed patients with progressive metastatic castration resistant prostate cancer (mCRPC) who were treated with at least two cycles of 177Lu-PSMA-617 at our institution from June 2022 to June 2023. Post-therapy whole-body digital SPECT/CT (GE StarGuide) was performed from vertex to mid-thigh at 1-2 hours after 177Lu-PSMA-617 infusion. Post-therapy SPECT/CT images were quantified with MIM software. Lu177-PSMA positive lesions were delineated with liver parenchyma uptake as cut-off. Lu-PSMA positive total tumor volume (Lu-TTV), tumor SUVmax and SUVmean were obtained. Post-therapy SPECT/CT image after cycle 1 was used as baseline for comparison with SPECT/CT after cycle 2 and 3. Overall survival, PSA progression free survival (PSA-PFS) as defined by PCWG3 and PSA decline &gt; 50% from baseline (PSA50) at any time after treatment were measured. Changes in post-therapy SPECT/CT were correlated with clinical outcomes to assess quantitative SPECT/CT as a tool for early treatment response. Analyses were performed with SPSS. Results: A total of 56 patients (76±8, mean ± SD, range 60-93 years old) who were imaged with at least 2 post-therapy SPECT/CT were included in the analysis. Post-therapy whole body SPECT/CT was acquired in ~12 mins. All scanned patients tolerated the rapid whole-body SPECT/CT very well. With median follow up of 10 months, median PSA-PFS was 5.0 months (range 1.0-15 months), 33 of 56 patients (58.9%) achieved PSA50 at any time after treatment, and 42 of 56 patients (75%) were alive at data cutoff. Quantitative analysis of SPECT/CT images showed that 36 of 56 patients (64%) had a &gt;30% decrease in Lu-TTV on early follow-up post-therapy SPECT/CT after cycle 2 or 3. Kaplan-Meier survival analysis showed that a &gt;30% decrease in Lu-TTV was associated with longer overall survival (median not reached vs 6 months, P = 0.008) and longer PSA-PFS (6 months vs 1 months, P &lt; 0.001). Decrease in SUVmax or SUVmean, however, was not associated with PSA-PFS or overall survival. Conclusions: Rapid post-therapy whole-body digital SPECT/CT was well tolerated in post-therapy SPECT/CT imaging following 177Lu-PSMA-617 treatment. Quantitation of post-therapy SPECT/CT may be useful in evaluating early treatment response of 177Lu-PSMA-617. Prospective validation and larger patient cohorts are needed to further elucidate the role of post-therapy SPECT/CT imaging in guiding patient management in 177Lu-PSMA-617 therapy.

Abstract TMP109: Elovanoid Precursors Are Neuroprotective in Experimental Ischemic Stroke

Objective: Ischemic stroke triggers oxidative and biochemical responses that disrupt cell homeostasis. We previously demonstrated that Elovanoids (ELVs), a novel class of homeostatic lipid mediators, reduced infarct volumes and improved neurologic function when administered IV following middle cerebral artery occlusion (MCAo). The present study defines neuroprotection by very long-chain polyunsaturated fatty acid (VLC-PUFA) ELV precursors (C-32:6 and C-34:6) delivered intranasally following experimental ischemic stroke. Methods: Male SD rats underwent 2 hours of MCAo. Treatments with C-32:6, C-34:6 (1μg/μl, 20 μg per rat), or vehicle were administered at 1, 24, and 48h after onset of MCAo. Behavior testing was performed on days 1, 2, 3, and 7. Ischemic core and penumbra were computed from T2WI on day 7 followed by immunohistochemistry. RT-qPCR gene expression was investigated in a separate cohort of rats treated as above at 72 h. Results: C-32:6 and C-34:6 improved behavioral function on days three by (41% and 20%) and seven by (45% and 24%); T2WI total lesion volumes were reduced by (87% and 61%), respectively, compared to the vehicle. In the ischemic penumbra, C-32:6 and C-34:6 reduced TMEM119 + microglia by (38% and 29%), increased NeuN + neurons by (87% and 110%), reduced IgG staining by (54% and 25%), and increased the number of SMI-71 + vessels by (50% and 26%). In the core, C-32:6 and C-34:6 reduced TMEM119 + microglia by (12% and 15%), increased NeuN + neurons by (251% and 89%) and increased the number of SMI-71 + vessels by (31% and 70%). Anti-inflammatory marker genes for protective microglia and astrocyte phenotypes Tm4sf1, Thbs1, Ptx3, Gpc4, Fizz1, Cd14, Msr1, Manf , and Osmr were upregulated with C-32:6 and genes Fcrls, S1pr3, and Vim were downregulated with C-34:6. Conclusion: These data suggest that IN administered C-32:6 C-34:6 improved behavior, protected the ischemic penumbra, increased neurogenesis and angiogenesis, and reduced the number of microglia cells. The overall gene expression changes observed from free fatty acid C-32:6 indicate that its modulatory effects promote the biological activity of astrocytes, microglia, and cerebrovascular cells involved in plasticity.

Origin of domesticated water chestnuts (Trapa bispinosa Roxb.) and genetic variation in wild water chestnuts

AbstractThe water chestnut Trapa bispinosa Roxb. has been domesticated in China and has been reported as the only domesticated species of this genus. To understand the origin of T. bispinosa and its evolution pathway, we compared the genetic similarity and seed morphology of domesticated water chestnut T. bispinosa with three wild species T. natans, T. incisa, and T. japonica along with archeological seed samples from the Tianluoshan site (approximately 7000–6300 cal BP) in China. The largest seed size was observed only in the domesticated species, whereas other wild species showed smaller size including T. natans L. genetically close to the domesticated type, and T. incisa was the smallest in size. The volumes of the seed capsule and endosperm were measured using X ray CT scans, showing the ratios of total volumes between T. bispinosa and wild species ranged from 4.2 to 4.5. The ratios of endosperm volume ranged from 3.3 to 3.7. Both measurements showed domesticated species have larger seed volume. Genome size was indirectly estimated by flow cytometry. Domesticated species with larger seed size was estimated as diploid, as were the wild species except for tetraploid species T. japonica. Domesticated species clearly showed the largest edible organs, but it was not a result of ploidy level changes. Maternal lineages traced using complete whole chloroplast sequences, suggested that T. natans is the closest to T. bispinosa, both of which are close to T. japonica. The result was confirmed by PCR genotyping with chloroplast insertion/deletion (cpINDEL) markers developed in the study. T. incisa showed distinct plastid types within the species, and T. japonica showed a unique plastid genotype. Our study concludes the largest volumes for the edible endosperm have been accomplished through nearly 6000 years of artificial selection, but the domestication did not involve ploidy level changes.

Physical Activity Intensity and Risk of Dementia

IntroductionRegular participation in aerobic physical activity is associated with a reduced risk of dementia. It is currently unclear whether this association is due to the total volume or intensity of physical activity. MethodsThis prospective cohort study analyzed 386,486 adults from the UK Biobank who were free of dementia and self-reported >0 minutes of moderate-to-vigorous intensity physical activity (MVPA) at baseline (2007-2010). Participants were categorized as performing 0%, >0% to 30%, or >30% of their total MVPA in vigorous activity (VPA). Cox proportional hazards regression models were used to examine the associations between categories of VPA and incident dementia while adjusting for sociodemographic and lifestyle factors including total MVPA. Analyses were performed in 2022. ResultsOver an average follow-up of 12.0 (1.7) years, there were 5,177 (1.3%) cases of dementia. Compared to the group reporting 0% VPA, the hazard ratios (95% confidence intervals) of dementia for the groups reporting >0% to 30% and >30% VPA were 0.73 (0.68-0.78) and 0.81 (0.75-0.87), respectively, in the fully adjusted model. In a joint analysis, reporting some VPA was associated with a reduced risk of dementia regardless of meeting the aerobic physical activity guidelines (HR=0.78 [0.72-0.85]) or not (HR=0.76 [0.60-0.98]), while meeting the aerobic physical activity guidelines alone without VPA was not associated with incident dementia (HR=0.98 [0.90-1.07]), compared to the group that did not meet the guidelines and reported no VPA. ConclusionsThese results suggest that engaging in VPA as part of MVPA is associated with a lower risk of dementia.