Total Lesion Volume Research Articles

The effect of total size, area, and volume of lesions in multifocal/multicentric breast cancers and unifocal breast cancers on survival: An observational study.

In this study, we aimed to investigate the prognostic effect of the classifications made according to the stage of the largest lesion diameter (T-max stage) and of the sum of the longest diameters of the lesions (T-sum stage), the largest area stage (A-max stage), the sum of the largest areas (A-sum stage), the highest volume stage (V-max stage), the sum of the highest volume (V-sum stage) on disease-free survival, and overall survival (OS) in multifocal/multicentric breast cancers (MMBCs) and unifocal breast cancers (UBCs). The study included a total of 769 patients either with MMBC (n = 128) or UBC (n = 641) who underwent surgery between 2006 and 2015. In the analysis, the median age of 769 patients was 53.0 (20.0-94.0) years, and 16.6% of these 769 patients were MMBC and 83.4% were UBC. In multivariate analysis, lymphovascular invasion (LVİ), estrogen receptor, and nodal status were common independent prognostic factors, whereas T-max stage [(HR: 1.17) (CI 95%: 1.03-1.33) (P = .018)] was a prognostic factor for OS. In multivariate analysis, the T-max stage is an independent risk factor for OS. Therefore, T-max should be continued to be used for measurement and T-stage should be used for classification in MMBCs/UBCs.

Cerebrovascular pulsatility indicates preoperative subcortical cognitive impairment and an increased risk for postoperative delirium in elderly patients undergoing elective spine surgery.

Advances in spine surgery enable safe interventions in elderly patients, but perioperative neurocognitive disorders (pNCD), such as post-operative delirium (POD) and cognitive dysfunction (POCD), remain a serious concern. Pre-operative cognitive impairment is a major risk factor for pNCD. Comprehensive pre-operative cognitive assessments are not feasible in clinical practice, making effective screening methods desirable. This study investigates whether pre-operative cerebrovascular duplex sonography can assess subcortical (vascular) cognitive impairment and the risk for POD. This prospective single-center study recruited patients aged ≥60 years scheduled for elective spine surgery at a German university hospital. Patients underwent pre-operative assessments including cognitive abilities (CERAD test battery), structural MRI, and cerebrovascular duplex sonography. POD screening was conducted three times daily for at least 3 days. The primary hypothesis, that the mean pulsatility index (PI) of both internal carotid arteries (ICA) predicts POD risk, was tested using logistic regression. Secondary analyses examined the association between POD risk and ICA flow (time-averaged peak velocities, TAPV) and correlations with cognitive profiles and MRI characteristics. POD occurred in 22% of patients (n = 22/99) within three postoperative days. Patients with POD were significantly older (75.9 ± 5.4 vs. 70.0 ± 6.9 years, p < 0.01) but did not differ by gender (p = 0.51). ICA PI significantly predicted POD risk (OR = 5.46 [95%CI: 1.81-16.49], p = 0.003), which remained significant after adjustment for age and duration of surgery (ORadj = 6.38 [95% CI: 1.77-23.03], p = 0.005). TAPV did not inform the POD risk (p = 0.68). ICA PI Pre-operative cognitive scores were significantly associated with ICA PI (mean CERAD score: r = -0.32, p < 0.001). ICA PI was also significantly associated with total white matter lesion volume (τ = 0.19, p = 0.012) and periventricular white matter lesion volume (τ = 0.21, p = 0.007). This is the first study to demonstrate that cerebrovascular duplex sonography can assess the risk for POD in elderly spine surgery patients. Increased ICA PI may indicate subcortical impairment, larger white matter lesion load, and lower white matter volume, predisposing factors for POD. Pre-operative cerebrovascular duplex sonography of the ICA is widely available, easy-to-use, and efficient, offering a promising screening method for POD risk. Increased ICA PI could supplement established predictors like age to adjust surgical and peri-operative procedures to individual risk profiles.

Nd-YAG laser-assisted pulmonary metastasectomy: initial experience from a tertiary care cancer center in India.

Pulmonary metastasectomy is recommended for metastatic lung lesions when R0 resection is possible, the primary site is in controlled status, surgery is of low risk, and extrathoracic metastases are absent. We present the initial experiences of laser-assisted surgery (LAS) for pulmonary metastatic lesions from a tertiary care cancer center in India. All patients undergoing non-anatomical pulmonary metastasectomy between September 2022 and January 2023 for synchronous and metachronous lesions, operated on by a single consultant thoracic oncosurgeon in a tertiary care center of India, were identified from a prospective database. Ten patients with 124 metastatic lesions were included in the study. A hybrid approach (video-assisted thoracoscopic surgery (VATS) with mini-thoracotomy) was performed. Measurements of total lesion volume and lung parenchyma resected were taken from the final histopathological analysis of the intraoperative sample. LAS was performed for 102 lesions and stapled wedge resection for 22 lesions. Evidence of malignancy was noted in 88/102 (86.3%) of the lesions excised. Patients with LAS had advantages of parenchyma preservation, less postoperative morbidities, and shorter hospital stays. LAS of pulmonary metastatic lesions addresses more lesions in a single sitting; the bilateral lung lesions can be operated and has parenchyma preserving and good sealant properties. The online version contains supplementary material available at 10.1007/s12055-024-01723-8.

Impact of repositioning on brain injury following transcatheter aortic valve replacement with a self-expanding valve

Repositionable self-expanding valves allow for repositioning during deployment to achieve optimal valve placement. However, the risk of brain injury associated with repositioning, as detected by diffusion-weighted magnetic resonance imaging (DW-MRI), is unknown. Consecutive patients undergoing transcatheter aortic valve replacement (TAVR) with repositionable self-expanding valves and receiving DW-MRI before and within 7 days post-TAVR procedure were included. The primary outcomes were incidence, number, total volume, and volume per lesion of the cerebral ischemic lesion in DW-MRI after TAVR. Univariate and multivariate logistic regression assessed the association between repositioning and bigger total lesion volume (> 1 cm3 or > 0.5 cm3). Negative binomial regressions were performed to explore the association between repositioning and number of lesions. A propensity score matching was performed to adjust the potential confounders. Moreover, inverse probability of treatment weighted regression model with nonstabilized weights was used as sensitivity analysis. Among 243 included patients, repositioning was performed in 116 (47.7%) patients. The incidence of overt stroke (1.7% vs. 1.6%, p = 0.927) and silent stroke (86.2% vs. 85.8%, p = 0.932) were comparable between two groups. However, the number of new lesions (5.0 [2.0–9.0] vs. 3.0 [2.0–6.0], p = 0.048), and total lesion volume (275.0 [90.0–947.5] mm3 vs. 180.0 [50.0–440.0] mm3, p = 0.022) were significantly higher in the repositioned group. Moreover, the proportion of patients with lesion size greater than 0.5 cm3 was higher in the repositioned group (37.9% vs. 22.0%, p = 0.007). The similar results were observed after propensity score matching. In both multivariate regression model and sensitivity analysis, the repositioning was the independent predictor of number of lesions and bigger total lesion volume after TAVR. The utilization of the repositioning feature may increase the number and volume of silent brain infarcts in DW-MRI in patients who underwent TAVR. (Transcatheter Aortic Valve Replacement Single Center Registry in Chinese Population [TORCH]; NCT02803294)

Structural and molecular imaging-based characterization of soft tissue and vascular calcification in hyperphosphatemic familial tumoral calcinosis.

Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare disorder caused by deficient FGF23 signaling and resultant ectopic calcification. Here, we systematically characterized and quantified macro- and micro-calcification in a HFTC cohort using CT and 18F-sodium fluoride PET/CT (18F-NaF PET/CT). Fourier-transform infrared (FTIR) spectroscopy was performed on 4 phenotypically different calcifications from a patient with HFTC, showing the dominant component to be hydroxyapatite. Eleven patients with HFTC were studied with CT and/or 18F-NaF PET/CT. Qualitative review was done to describe the spectrum of imaging findings on both modalities. CT-based measures of volume (eg, total calcific burden and lesion volume) and density (Hounsfield units) were quantified and compared to PET-based measures of mineralization activity (eg, mean standardized uptake values-SUVs). Microcalcification scores were calculated for the vasculature of 6 patients using 18F-NaF PET/CT and visualized on a standardized vascular atlas. Ectopic calcifications were present in 82% of patients, predominantly near joints and the distal extremities. Considerable heterogeneity was observed in total calcific burden per patient (823.0 ± 670.1cm3, n = 9) and lesion volume (282.5 ± 414.8cm3, n = 27). The largest lesions were found at the hips and shoulders. 18F-NaF PET offered the ability to differentiate active vs quiescent calcifications. Calcifications were also noted in multiple anatomic locations, including brain parenchyma (50%). Vascular calcification was seen in the abdominal aorta, carotid, and coronaries in 50%, 73%, and 50%, respectively. 18F-NaF-avid, but CT-negative calcification was seen in a 17-year-old patient, implicating early onset vascular calcification. This first systematic assessment of calcifications in a cohort of patients with HFTC has identified the early onset, prevalence, and extent of calcification. It supports 18F-NaF PET/CT as a clinical tool for distinguishing between active and inactive calcification, informing disease progression, and quantification of ectopic and vascular disease burden.

Perihaematomal Oedema Evolution over 2 Weeks after Spontaneous Intracerebral Haemorrhage and Association with Outcome: A Prospective Cohort Study.

We know little about the evolution of perihaematomal oedema (PHO) &gt;24 h after ICH onset. We aimed to determine the trajectory of PHO after ICH onset and its association with outcome. We did a prospective cohort study using a pre-specified scanning protocol in adults with first-ever spontaneous ICH and measured absolute PHO volumes on CT head scans at ICH diagnosis and 3 ± 2, 7 ± 2, and 14 ± 2 days after ICH onset. We used the largest ICH if ICHs were multiple. The primary outcomes were (a) the trajectory of PHO after ICH onset and (b) the association between PHO (absolute volume at the time when most repeat CT head scans were obtained, and change in PHO volume at this time compared with the first CT head scan) and poor functional outcome (modified Rankin scale 3-6 at 90 days). We pre-specified multivariable logistic regression models of this association adjusting analyses for potential confounders: age, GCS, infratentorial ICH location, and intraventricular extension. In 106 participants of whom 49 (46%) were female, with a median ICH volume 7 mL (interquartile range [IQR] 2-22 mL), the trajectory of median PHO volume increased from 14 mL (IQR: 7-26 mL) at diagnosis to 18 mL (IQR: 8-40 mL) at 3 ± 2 days (n = 87), 20 mL (IQR: 8-48 mL) at 7 ± 2 days (n = 93) and 21 mL (IQR: 10-54 mL) at 14 ± 2 days (n = 78) (p = &lt;0.001). PHO volume at each time point was collinear with ICH volume at diagnosis (│r│ &gt;0.7), but the change in PHO volume between diagnosis and each time point was not. Given collinearity, we used total lesion (i.e., ICH + PHO) volume instead of PHO volume in a logistic regression model of its association at each time point with outcome. Increasing total lesion (ICH + PHO) volume at day 7 ± 2 was associated with poor functional outcome (adjusted OR per mL 1.02, 95% CI: 1.00-1.03; p = 0.036), but the increase in PHO volume between diagnosis and day 7 ± 2 was not associated with poor functional outcome (adjusted OR per mL 1.03, 95% CI: 0.99-1.07; p = 0.132). PHO volume increases throughout the first 2 weeks after onset of mild to moderate ICH. Total lesion (ICH + PHO) volume at day 7 ± 2 was associated with poor functional outcome, but the change in PHO volume between diagnosis and day 7 ± 2 was not. Prospective cohort studies with larger sample sizes are needed to investigate these associations and their modifiers.

The association of structural versus load-dependent large artery stiffness mechanisms with cerebrovascular damage and cortical atrophy in humans.

Large central arterial stiffness is a risk factor for cerebrovascular damage and subsequent progression of neurodegenerative diseases, including Alzheimer's disease and dementia. However, arterial stiffness is determined by both the intrinsic components of the arterial wall (structural stiffness) and the load (i.e., arterial blood pressure) exerted upon it by the blood (load-dependent stiffness). This study aimed to determine the degree to which structural and/or load-dependent mechanisms of central arterial stiffness are associated with cerebrovascular damage. Among 128 healthy individuals (aged 63±6, age range: 50-80 years, 42% men), aortic and carotid artery stiffness was measured via carotid-femoral pulse wave velocity and B-mode ultrasonography, respectively. Using participant-specific exponential models, both aortic and carotid artery stiffness were standardized to a reference blood pressure to separate their structural and load-dependent stiffness mechanisms. Magnetic resonance imaging was used to derive total, periventricular, and deep cerebral white matter lesion volume (WMLV) and global cortical thickness. After adjusting for common cardiovascular disease risk factors, a 1 m/s increase in structural aortic stiffness was associated with 15% greater total WMLV (95% confidence interval [CI] = 0.01, 0.27, P = 0.036), 14% greater periventricular WMLV (95%CI = 0.004, 0.25, P = 0.044) and 0.011mm lower cortical thickness (95%CI = -0.022, -1.18, P = 0.028). No association was observed between structural carotid stiffness and WMLVs (total, periventricular, and deep), and neither aortic nor carotid load-dependent stiffness was associated with WMLVs or cortical thickness. Structural, not load-dependent, mechanisms of aortic stiffness are related to cerebrovascular-related white matter damage.

Automatic lesion detection at Multiple Sclerosis patients – Comparison of 2D- and 3D-FLAIR-datasets

BackgroundMultiple Sclerosis (MS) is a common autoimmune inflammatory disease of the central nervous system (CNS). Magnetic Resonance Imaging (MRI) allows a sensitive assessment of the CNS and is established for diagnostic, prognostic and (therapy-) monitoring purposes. Especially lesion counting in T2- or Fluid Attenuated Inversion Recovery (FLAIR)-weighted images plays a decisive role in clinical routine. Software-packages allowing an automatic evaluation of image data are increasingly established aiming a faster and improved workflow. These programs allow e.g. the counting, spatial attribution and volumetry of MS-lesions in FLAIR-weighted images. Research has shown that 3D-FLAIR-sequences are superior to 2D-FLAIR-sequences in visual evaluation of lesion burden in MS. An influence on the automatic analysis is expectable but not yet systematically studied. This work will therefore investigate the influence of 2D- and 3D datasets on the results of an automatic assessment. Material and methodsIn this prospective study, 80 Multiple Sclerosis patients underwent a clinically indicated routine MRI examination. The clinical routine protocol already including a 3D-FLAIR sequence was adapted by an additional 2D-FLAIR sequence also conform to the 2021 MAGNIMS-CMSCNAIMS consensus recommendations. To obtain a quantitative analysis for assessment of amount, dissemination and volume of the lesions, the acquired MR images were post-processed using the CE-certified Software mdbrain (mediaire, Berlin, Germany). The resulting data were statistically analysed using the paired t-test for normally distributed data and the Wilcoxon-signed-rank-test for not normally distributed data respectively. Demographic data and data such as the subtype, duration, severity and therapy of the disease were collected, pseudonymized and evaluated. ResultsThere is a significant difference concerning the total number and lesion volume with more lesions being detected (2D: 29.7, +/- 20.22 sd; 3D: 40.1 +/- 31.67 sd; p < 0.0001) but lower total volume (2D: 6.24 +/- 6.11 sd; 3D: 5.39 +/- 6.37 sd; p < 0.0001) when using the 3D- sequence. Especially significantly more small lesions in the unspecific white matter and infratentorial region were detected by using the 3D-FLAIR sequence (p < 0.0001) compared to the 2D-FLAIR image. Main reason for the lower total volume in the 3D-FLAIR sequence was the calculated volume for periventricular lesions which was significantly beneath the calculated volume from the 2D-FLAIR sequence (p < 0.0001). ConclusionAutomatic lesion counting and volumetry is feasible with both 2D- and 3D-weightend FLAIR images. Still, it leads to partly significant differences even between two sequences that both are conform to the 2021 MAGNIMS-CMSCNAIMS consensus recommendations. This study contributes valuable insights into the impact of using different input data from the same patient for automated MS lesion evaluation.

Brain lesion microstructure in neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein disease.

Neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) diagnosis are based on the presence of serological and magnetic resonance imaging (MRI) biomarkers. Diffusion tensor imaging (DTI), neurites orientation dispersion and density imaging (NODDI), and the Spherical Mean Technique (SMT) may be helpful to provide a microstructural characterization of the different types of white matter lesions and give an insight about their different pathological mechanisms. The aim of the study was to characterize microstructural differences between brain typical lesions (TLs) and nontypical lesions (nTLs). A total of 17 NMOSD and MOGAD patients [9 Aquaporin4 (AQP4)+NMO, 2 seronegative-NMO, 6 MOGAD] underwent MRI scans on a 3 Tesla MAGNETON PRISMA. Diffusion parameters (fractional anisotropy; mean diffusivity [MD]; intracellular volume fraction [ICVF]; extra-neurite transverse diffusivity; and extra-neurite MD; neurite signal fraction) were obtained using DTI, NODDI, and SMT. Microstructural parameters within lesions were compared through a generalized linear model using age, sex, and total lesion volume as covariates. In NMOSD/MOGAD whole cohort (total lesions=477), TLs showed increased MD and decreased ICVF compared to nTLs (p<.05), indicating higher inflammation and axonal loss. Similar results were found also in the AQP4+NMO subgroup (decreased ICVF, p<.05). Furthermore, in NMOSD/MOGAD whole cohort and in AQP4+NMO subgroup, TLs showed a trend toward higher EXRATRANS than nTLs, suggesting a more severe degree of demyelination within TLs. TLs and nTLs in NMOSD/MOGAD showed different diffusion MRI-derived microstructural features, with TLs showing a more severe degree of inflammation and fiber disruption with respect to nTLs.

Different extramedullary disease shown in chemokine receptor 4 targeted PET/CT with [ 68 Ga]Ga-pentixafor in patients with Waldenström macroglobulinemia and smoldering disease.

It is important to distinguish Waldenström macroglobulinemia from smoldering Waldenström macroglobulinemia (sWM), because only patients with Waldenström macroglobulinemia require treatment, however the distinction can be clinically complex. The aim of this study is to investigate whether [ 68 Ga]Ga-pentixafor PET/CT shows different characteristics in sWM and Waldenström macroglobulinemia patients and therefore can help to differentiate Waldenström macroglobulinemia and sWM. Thirty-seven patients with newly diagnosed Waldenström macroglobulinemia and 11 sWM patients were analyzed [35 men and 13 women; 64.3 ± 10.7 (range, 29-87) years old]. The SUV max of bone marrow disease, lymph nodes, and other extramedullary diseases on [ 68 Ga]Ga-pentixafor were significantly higher than those on 2-[ 18 F]FDG PET/CT ( P < 0.05). On [ 68 Ga]Ga-pentixafor PET/CT, patients with Waldenström macroglobulinemia had more lymph node regions involved, significantly higher incidence of involvement in more than three lymph node regions, larger nodal disease, and higher incidence of other extramedullary disease when compared with sWM patients ( P < 0.05). Waldenström macroglobulinemia patients showed significantly higher total lesions uptake, total lesion volume, and SUV max of extramedullary disease than sWM patients did ( P < 0.05). None of the visual or semiquantitative indexes in 2-[ 18 F]FDG PET/CT showed significant difference between Waldenström macroglobulinemia and sWM patients. [ 68 Ga]Ga-pentixafor PET/CT had better diagnostic performance than 2-[ 18 F]FDG PET/CT in Waldenström macroglobulinemia. Patients with Waldenström macroglobulinemia presented with more extensive extramedullary disease shown in [ 68 Ga]Ga-pentixafor PET/CT than sWM patients did.

Neighborhood disadvantage is associated with working memory and hippocampal volumes among older adults

ABSTRACT It is not well understood how neighborhood disadvantage is associated with specific domains of cognitive function and underlying brain health within older adults. Thus, the objective was to examine associations between neighborhood disadvantage, brain health, and cognitive performance, and examine whether associations were more pronounced among women. The study included 136 older adults who underwent cognitive testing and MRI. Neighborhood disadvantage was characterized using the Area Deprivation Index (ADI). Descriptive statistics, bivariate correlations, and multiple regressions were run. Multiple regressions, adjusted for age, sex, education, and depression, showed that higher ADI state rankings (greater disadvantage) were associated with poorer working memory performance (p < .01) and lower hippocampal volumes (p < .01), but not total, frontal, and white matter lesion volumes, nor visual and verbal memory performance. There were no significant sex interactions. Findings suggest that greater neighborhood disadvantage may play a role in working memory and underlying brain structure.

Association between renal insufficiency and lesion characteristics of posterior reversible encephalopathy syndrome.

Posterior reversible encephalopathy syndrome (PRES) is characterized by cerebral blood flow dysregulation and the blood-brain barrier (BBB) disruption. While renal insufficiency has been considered a factor in BBB fragility, the relationship between renal insufficiency and the PRES lesions volume remains unclear. This observational study was performed retrospectively. PRES patients were categorized into two groups with renal insufficiency, defined as an estimated glomerular filtration rate (eGFR) of less than 60mL/min/1.73m2 on the day of symptom occurrence. Lesion volume was measured using fluid-attenuated inversion recovery (FLAIR) imaging, and the brain was divided into nine regions. The volume of the parietal-occipital-temporal lobe was considered typical, while the other six regions were labeled as atypical. The study included 200 patients, of whom 94 (47%) had renal insufficiency. Patients with renal insufficiency had a larger lesion volume (144.7 ± 125.2cc) compared to those without renal insufficiency (110.5 ± 93.2cc; p = 0.032); particularly in the atypical lesions volume (49.2 ± 65.0 vs. 29.2 ± 44.3cc; p = 0.013). However, there was no difference in the reversibility of the lesions (35.2 ± 67.5 vs. 18.8 ± 33.4cc; p = 0.129). Multiple regression analysis revealed that decreases in eGFR (β = -0.34, 95% CI -0.62-0.05, p = 0.020) were positively associated with total lesion volume. Our findings suggest that PRES patients with renal insufficiency experience more severe lesion volumes, likely due to the atypical brain regions involvement. The lesions involving atypical regions may have a similar pathophysiology to typical lesions, as the PRES lesions reversibility was found to be similar between individuals with and without renal insufficiency.

The impact of paramagnetic rim lesions on cortical thickness and gray to white matter contrast in relapsing-remitting multiple sclerosis.

Paramagnetic rim lesions (PRLs) on susceptibility magnetic resonance sequences have been suggested as an imaging marker of disease progression in multiple sclerosis. This retrospective cross-sectional study aimed to investigate the impact of PRLs on cortical thickness and gray matter (GM) to white matter (WM) contrast in relapsing-remitting multiple sclerosis (RRMS). A total of 82 RRMS patients (40 patients with at least 1 PRL and 42 patients without PRL) and 43 healthy controls (HC) were included in this study. The T1-weighted images (T1WI) were processed with the FreeSurfer pipeline. GM to WM signal intensity ratio (GWR) was obtained from T1WI by dividing the GM signal intensity by the WM signal intensity for each vertex. Group differences in cortical thickness and GWR were tested on reconstructed cortical surface. Compared to HC, patients with PRL had thinner mean cortical thickness (P<0.001), higher mean GWR (P=0.001), and lower brain structure volumes (cortex volume, P=0.001; WM volume, P<0.001; deep GM volume, P<0.001). Vertex-based analysis found significant cortical thinning in several regions and increased GWR in a wider range of regions in patients with PRL. The two types of clusters had both overlapping regions and independent regions. However, in patients without PRL, only a few regions showed significant cortical thickness changes. Correlation analysis found that in patients with PRL, only PRL volume showed a significant negative correlation with mean cortical thickness (P=0.048), and PRL volume and count, non-PRL count, and total lesion volume were significantly and positively correlated with mean GWR (P<0.05). There were significant changes in cortical thickness, GWR, and brain structure volume in RRMS patients with PRL that may contribute to further understanding of the pathological mechanisms underlying neurological tissue damage.

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]

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.

Psychometric evaluation of the 5-item Medication Adherence Report Scale questionnaire in persons with multiple sclerosis.

The 5-item Medication Adherence Report Scale (MARS-5) is a reliable and valid questionnaire for evaluating adherence in patients with asthma, hypertension, and diabetes. Validity has not been determined in multiple sclerosis (MS). We aimed to establish criterion validity and reliability of the MARS-5 in persons with MS (PwMS). Our prospective study included PwMS on dimethyl fumarate (DMF). PwMS self-completed the MARS-5 on the same day before baseline and follow-up brain magnetic resonance imaging (MRI) 3 and 9 months after treatment initiation and were graded as highly and medium adherent upon the 24-cut-off score, established by receiver operator curve analysis. Health outcomes were represented by relapse occurrence from the 1st DMF dispense till follow-up brain MRI and radiological progression (new T2 MRI lesions and quantitative analysis) between baseline and follow-up MRI. Criterion validity was established by association with the Proportion of Days Covered (PDC), new T2 MRI lesions, and Beliefs in Medicines questionnaire (BMQ). The reliability evaluation included internal consistency and the test-retest method. We included 40 PwMS (age 37.6 ± 9.9 years, 75% women), 34 were treatment-naive. No relapses were seen during the follow-up period but quantitative MRI analysis showed new T2 lesions in 6 PwMS. The mean (SD) MARS-5 score was 23.1 (2.5), with 24 PwMS graded as highly adherent. The higher MARS-5 score was associated with higher PDC (b = 0.027, P<0.001, 95% CI: (0.0134-0.0403)) and lower medication concerns (b = -1.25, P<0.001, 95% CI: (-1.93-(-0,579)). Lower adherence was associated with increased number (P = 0.00148) and total volume of new T2 MRI lesions (P = 0.00149). The questionnaire showed acceptable internal consistency (Cronbach α = 0.72) and moderate test-retest reliability (r = 0.62, P < 0.0001, 95% CI: 0.33-0.79). The MARS-5 was found to be valid and reliable for estimating medication adherence and predicting medication concerns in persons with MS.

Segmentation of pre- and posttreatment diffuse glioma tissue subregions including resection cavities.

Evaluating longitudinal changes in gliomas is a time-intensive process with significant interrater variability. Automated segmentation could reduce interrater variability and increase workflow efficiency for assessment of treatment response. We sought to evaluate whether neural networks would be comparable to expert assessment of pre- and posttreatment diffuse gliomas tissue subregions including resection cavities. A retrospective cohort of 647 MRIs of patients with diffuse gliomas (average 55.1 years; 29%/36%/34% female/male/unknown; 396 pretreatment and 251 posttreatment, median 237 days post-surgery) from 7 publicly available repositories in The Cancer Imaging Archive were split into training (536) and test/generalization (111) samples. T1, T1-post-contrast, T2, and FLAIR images were used as inputs into a 3D nnU-Net to predict 3 tumor subregions and resection cavities. We evaluated the performance of networks trained on pretreatment training cases (Pre-Rx network), posttreatment training cases (Post-Rx network), and both pre- and posttreatment cases (Combined networks). Segmentation performance was as good as or better than interrater reliability with median dice scores for main tumor subregions ranging from 0.82 to 0.94 and strong correlations between manually segmented and predicted total lesion volumes (0.94 < R 2 values < 0.98). The Combined network performed similarly to the Pre-Rx network on pretreatment cases and the Post-Rx network on posttreatment cases with fewer false positive resection cavities (7% vs 59%). Neural networks that accurately segment pre- and posttreatment diffuse gliomas have the potential to improve response assessment in clinical trials and reduce provider burden and errors in measurement.

Differentiating multiple sclerosis from non-specific white matter changes using a convolutional neural network image classification model

BackgroundThe diagnosis of multiple sclerosis (MS) relies heavily on neuroimaging with magnetic resonance imaging (MRI) and exclusion of mimics. This can be a challenging task due to radiological overlap in several disorders and may require ancillary testing or longitudinal follow up. One of the most common radiological MS mimickers is non-specific white matter disease (NSWMD). We aimed to develop and evaluate models leveraging machine learning algorithms to help distinguish MS and NSWMD. MethodsAll adult patients who underwent MRI brain using a demyelinating protocol with available electronic medical records between 2015 and 2019 at Cleveland Clinic affiliated facilities were included. Diagnosis of MS and NSWMD were assessed from clinical documentation. Those with a diagnosis of MS and NSWMD were matched using total T2 lesion volume (T2LV) and used to train models with logistic regression and convolutional neural networks (CNN). Performance metrices were reported for each model. ResultsA total of 250 NSWMD MRI scans were identified, and 250 unique MS MRI scans were matched on T2LV. Cross validated logistic regression model was able to use 20 variables (including spinal cord area, regional volumes, and fractions) to predict MS compared to NSWMD with 68.0% accuracy while the CNN model was able to classify MS compared to NSWMD in two independent validation and testing cohorts with 77% and 78% accuracy on average. ConclusionAutomated methods can be used to differentiate MS compared to NSWMD. These methods can be used to supplement currently available diagnostic tools for patients being evaluated for MS.

Characterization of white matter lesions in multiple sclerosis using proton density and T1-relaxation measures

PurposeAlthough lesion dissemination in time is a defining characteristic of multiple sclerosis (MS), there is a limited understanding of lesion heterogeneity. Currently, conventional sequences such as fluid attenuated inversion recovery (FLAIR) and T1-weighted (T1W) data are used to assess MS lesions qualitatively. Estimating water content could provide a measure of local tissue rarefaction, or reduced tissue density, resulting from chronic inflammation. Our goal was to utilize the proton spin density (PD), derived from a rapid, multi-contrast STAGE (strategically acquired gradient echo) protocol to characterize white matter (WM) lesions seen on T2W, FLAIR and T1W data. Materials and methodsTwenty (20) subjects with relapsing-remitting MS were scanned at 3 T using T1W, T2-weighted, FLAIR and strategically acquired gradient echo (STAGE) sequences. PD and T1 maps were derived from the STAGE data. Disease severity scores, including Extended Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC), were correlated with total, high PD and high T1 lesion volumes. A probability map of high PD regions and all lesions across all subjects was generated. Five perilesional normal appearing WM (NAWM) bands surrounding the lesions were generated to compare the median PD and T1 values in each band with the lesional values and the global WM. ResultsT1W intensity was negatively correlated with PD as expected (R = −0.87, p < 0.01, R2 = 0.756) and the FLAIR signal was suppressed for high PD volumes within the lesions, roughly for PD ≥ 0.85. The threshold for high PD and T1 regions was set to 0.909 and 1953.6 ms, respectively. High PD regions showed a high probability of occurrence near the boundary of the lateral ventricles. EDSS score and nine-hole peg test (dominant and non-dominant hand) were significantly correlated with the total lesion volume and the volumes of high PD and T1 regions (p < 0.05). There was a significant difference in PD/T1 values between the high PD/T1 regions within the lesions and the remaining lesional tissue (p < 0.001). In addition, the PD values of the first NAWM perilesional band directly adjacent to the lesional boundary displayed a significant difference (p < 0.05) compared to the global WM. ConclusionLesions with high PD and T1s had the highest probability of occurrence at the boundary of the lateral ventricles and likely represent chronic lesions with significant local tissue rarefaction. Moreover, the perilesional NAWM exhibited subtly increasing PD and T1 values from the NAWM up to the lesion boundary. Unlike on the T1 maps, the perilesional band adjacent to the lesion boundary possessed a significantly higher PD value than the global WM PD values. This shows that PD maps were sensitive to the subtle changes in NAWM surrounding the lesions.

Alzheimer’s disease genetic risk score and neuroimaging biomarkers in the FINGER multidomain lifestyle randomized controlled trial

AbstractBackgroundA comprehensive genetic risk score (GRS) for Alzheimer’s disease (AD‐GRS) was recently developed based on 83 genome‐wide significant variants (Bellenguez et al. Nat Genet. 2022), excluding APOE. This study investigated AD‐GRS and APOE4 in relation to neuroimaging biomarkers in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER).MethodFINGER included at‐risk individuals without dementia from the general population, aged 60‐77 years. Participants were randomized to either 2‐year multidomain lifestyle‐based intervention or regular health advice. At baseline, 132 participants underwent MRI scans, of which 48 also underwent PET scans (PiB/FDG). Two years later, 112 and 39 repeated their scans, respectively. MRI measures included hippocampus, total gray matter and white matter lesion volumes, and cortical thickness. Composite indices were calculated for PiB and FDG uptake values. We report preliminary results from linear regressions (standardized β‐coefficients, p‐values).ResultAt baseline, higher AD‐GRS tended to relate to lower hippocampus volume (β = ‐0.15, p = 0.07) and FDG‐PET index (β = ‐0.23, p = 0.08); this remained after APOE adjustment. APOE4 was associated with lower hippocampus volume (β = ‐0.27, p = 0.001) and higher PiB‐PET index (β = 0.48, p = 0.001). Overall, AD‐GRS was not related to the 2‐year change in neuroimaging measures, while APOE4 was related to decreasing hippocampus (β = ‐0.27, p = 0.01) and total gray matter (β = ‐0.25, p = 0.01) volumes, and cortical thickness (β = ‐0.28, p = 0.003). There were no significant interactions of AD‐GRS or APOE4 with randomization group in relation to neuroimaging changes. However, in analyses stratified by AD‐GRS (below vs above median), there was less PIB index increase in intervention vs control in the higher AD‐GRS group (β = ‐0.60, p = 0.03); no intervention control‐difference was found in the lower AD‐GRS group (β = 0.04, p = 0.86). In analyses stratified by APOE4, PIB index tended to increase less in intervention vs control in non‐carriers (β = ‐0.38, p = 0.078), with no intervention‐control difference in carriers (β = 0.05, p = 0.89).ConclusionUnlike APOE4, AD‐GRS was not related to 2‐year change in AD‐related neuroimaging measures. AD‐GRS and APOE4 may also have very different impact on potential intervention effects on amyloid, i.e. less accumulation in the higher‐risk group (AD‐GRS) vs lower‐risk group (APOE). However, these exploratory findings need to be verified in larger studies.