MIM Software Research Articles

NIMG-85. RADIATION DOSE IS ASSOCIATED WITH CHANGE IN MAGNETIC RESONANCE FINGERPRINTING PROPERTIES OF ANATOMICALLY DISTINCT REGIONS OF INTEREST IN GLIOBLASTOMA MULTIFORME PATIENTS

Abstract Magnetic Resonance Fingerprinting (MRF) is an investigational imaging technique that provides spatially-resolved quantification of tissue properties, in contrast to qualitatively weighted conventional MR imaging. Intentional sequential variation of acquisition parameters throughout the MRF acquisition produces a unique quantitative signal timecourse for each tissue, which generates a spatial “fingerprint” for individual voxels. This study applies MRF to quantitatively correlate radiation dose with MR signal intensity changes, specifically T1, T2, and M0 maps across regions of interest (ROIs) that are involved in cognitive speed and processing. Three patients who underwent radiation therapy for resected glioblastoma multiforme participated in this study. MRF scans were conducted at pre-radiotherapy (pre-RT), mid-radiotherapy (mid-RT), and post-radiotherapy (post-RT) timepoints. ROIs (bilateral hippocampi, amygdalae, dorsolateral prefrontal cortices, and corpus callosum) were contoured and radiation dose to the ROI contours at mid-RT and post-RT timepoints were obtained using MIM treatment planning software (MIM Software, Beachwood, OH). Spearman’s rank correlation test was conducted in MATLAB (MATLAB R2024a, Natick, MA) for mean radiation dose to ROIs against MRF T1 relaxation time, T2 relaxation time, and M0 proton density. Mean radiation dose exhibited statistically significant correlation with absolute changes from pre-RT to post-RT T1 relaxation time, T2 relaxation time, and M0 proton density values across the ROIs. Mid-RT scans showed intermediate changes, suggesting a progressive alteration in tissue characteristics with accumulating radiation dose. The hippocampus and amygdala received lower radiation doses than other ROIs and exhibited less pronounced changes in T1, T2, and M0 values. These results demonstrate a novel application of MRF in quantitative characterization of imaging changes in anatomically distinct ROIs. The correlation between radiation dose and absolute changes in MRF signal values from pre-RT to post-RT MRF scans reflect progressive changes as a result of radiation exposure.

The value of semiquantitative PET features and end-of-therapy PET in grade 3B follicular lymphoma.

Grade 3B follicular lymphoma (G3BFL) is a rare lymphoma thought to sit on a continuum between low-grade FL and diffuse large B-cell lymphoma (DLBCL). The prognostic impact of quantitative positron emission tomography (PET) metrics such as total metabolic tumour volume (TMTV), total lesion glycolysis (TLG), and maximum standard uptake value (SUVmax) have been extensively analysed in FL and DLBCL, but G3BFL data are lacking. Here, we describe PET outcomes and radiomic characteristics in 46 G3BFL cases uniformly treated with R-CHOP (like) chemotherapy. Central semi-automated PET TMTV, TLG, and SUVmax analyses, using MIM software, were correlated with clinical outcomes and compared with published results in low-grade FL and DLBCL. In G3BFL, the end-of-treatment complete metabolic response was associated with improved progression-free survival (PFS; p = 0.002) and overall survival (OS; p = 0.04). G3BFL median TLG (1455) and SUVmax (16.50) sit between published values for low-grade FL (TLG: 1112, SUVmax: 11.3) and DLBCL (TLG: 3004, SUVmax: 24.35). No association between TMTV (>350 cm3) and survival was seen (PFS: p = 0.24; OS: p = 0.40). High SUVmax (>19.2) and TLG (>2760) both conferred inferior PFS but not OS (PFS: SUVmax p = 0.004; TLG p = 0.05). These data support the routine incorporation of PET radiomics at baseline and treatment response for G3BFL.

Patterns of Locoregional Pancreatic Cancer Recurrence After Total Neoadjuvant Therapy and Implications on Optimal Neoadjuvant Radiation Treatment Volumes

PurposeThis study aimed to generate a map of local recurrences after neoadjuvant chemotherapy and radiation (total neoadjuvant therapy [TNT]) followed by surgical resection for pancreatic ductal adenocarcinoma (PDAC). Such recurrence patterns will serve to inform radiation treatment planning volumes that should be given in the neoadjuvant setting. Methods and MaterialsLocoregional recurrences after TNT followed by surgery treated between 2009 and 2022 were radiologically identified. Recurrences were individually segmented using MIM software and complied in a single base scan. All contour compilations were used to create a threshold contour encompassing 80% of recurrences among all patients, head only, and body/tail only. The distance between organs at risk and the threshold contour were measured to design an optimal clinical target volume contour for patients treated with TNT. Recurrence patterns were also compared with existing adjuvant guidelines to assess coverage. ResultsA database of 484 patients managed with TNT for PDAC was queried. While locoregional recurrences were rare in this cohort, we identified 80 patients with either isolated locoregional or simultaneous local and distant recurrences. Patients with diagnostic imaging at the time of recurrence were identified. The majority of recurrences were partially in the field of published contouring guidelines or volumetric expansions off of vessels, and volumetric coverage was low for all. Common areas of recurrence include the aorticodiaphragmatic junction, retropancreatic duodenal nodal basin, and the region to the right of the superior mesenteric artery. A novel set of proposed neoadjuvant contours was designed to cover the central-most 80% of recurrences. ConclusionsThis is the largest collection of local/regional PDAC recurrences from a cohort of patients treated exclusively with TNT. Patterns of local/regional recurrence using TNT in PDAC vary significantly from those patients with PDAC treated with a surgery-first approach. Novel contouring guidelines presented in this study can help to ensure optimal coverage of high risk regions and avoid reliance on the current adjuvant guidelines to guide treatment planning.

Establishing a 4D-CT lung function related volumetric dose model to reduce radiation pneumonia

In order to study how to use pulmonary functional imaging obtained through 4D-CT fusion for radiotherapy planning, and transform traditional dose volume parameters into functional dose volume parameters, a functional dose volume parameter model that may reduce level 2 and above radiation pneumonia was obtained. 41 pulmonary tumor patients who underwent 4D-CT in our department from 2020 to 2023 were included. MIM Software (MIM 7.0.7; MIM Software Inc., Cleveland, OH, USA) was used to register adjacent phase CT images in the 4D-CT series. The three-dimensional displacement vector of CT pixels was obtained when changing from one respiratory state to another respiratory state, and this three-dimensional vector was quantitatively analyzed. Thus, a color schematic diagram reflecting the degree of changes in lung CT pixels during the breathing process, namely the distribution of ventilation function strength, is obtained. Finally, this diagram is fused with the localization CT image. Select areas with Jacobi > 1.2 as high lung function areas and outline them as fLung. Import the patient's DVH image again, fuse the lung ventilation image with the localization CT image, and obtain the volume of fLung different doses (V60, V55, V50, V45, V40, V35, V30, V25, V20, V15, V10, V5). Analyze the functional dose volume parameters related to the risk of level 2 and above radiation pneumonia using R language and create a predictive model. By using stepwise regression and optimal subset method to screen for independent variables V35, V30, V25, V20, V15, and V10, the prediction formula was obtained as follows: Risk = 0.23656–0.13784 * V35 + 0.37445 * V30-0.38317 * V25 + 0.21341 * V20-0.10209 * V15 + 0.03815 * V10. These six independent variables were analyzed using a column chart, and a calibration curve was drawn using the calibrate function. It was found that the Bias corrected line and the Apparent line were very close to the Ideal line, The consistency between the predicted value and the actual value is very good. By using the ROC function to plot the ROC curve and calculating the area under the curve: 0.8475, 95% CI 0.7237–0.9713, it can also be determined that the accuracy of the model is very high. In addition, we also used Lasso method and random forest method to filter out independent variables with different results, but the calibration curve drawn by the calibration function confirmed poor prediction performance. The function dose volume parameters V35, V30, V25, V20, V15, and V10 obtained through 4D-CT are key factors affecting radiation pneumonia. Establishing a predictive model can provide more accurate lung restriction basis for clinical radiotherapy planning.

Application of MR images in radiotherapy planning for brain tumor based on deep learning

Purpose Explore the function and dose calculation accuracy of MRI images in radiotherapy planning through deep learning methods. Methods 131 brain tumor patients undergoing radiotherapy with previous MR and CT images were recruited for this study. A new series of MRI from the aligned MR was firstly registered to CT images strictly using MIM software and then resampled. A deep learning method (U-NET) was used to establish a MRI-to-CT conversion model, for which 105 patient images were used as the training set and 26 patient images were used as the tuning set. Data from additional 8 patients were collected as the test set, and the accuracy of the model was evaluated from a dosimetric standpoint. Results Comparing the synthetic CT images with the original CT images, the difference in dosimetric parameters D98, D95, D2 and Dmean of PTV in 8 patients was less than 0.5%. The gamma passed rates of PTV and whole body volume were: 1%/1 mm: 93.96%±6.75%, 2%/2 mm: 99.87%±0.30%, 3%/3 mm: 100.00%±0.00%; and 1%/1 mm: 99.14%±0.80%, 2%/2 mm: 99.92%±0.08%, 3%/3 mm: 99.99%±0.01%. Conclusion MR images can be used both in delineation and treatment efficacy evaluation and in dose calculation. Using the deep learning way to convert MR image to CT image is a viable method and can be further used in dose calculation.

Evaluation and mitigation of deformable image registration uncertainties for MRI-guided adaptive radiotherapy.

We evaluate the performance of a deformable image registration (DIR) software package in registering abdominal magnetic resonance images (MRIs) and then develop a mechanical modeling method to mitigate detected DIR uncertainties. Three evaluation metrics, namely mean displacement to agreement (MDA), DICE similarity coefficient (DSC), and standard deviation of Jacobian determinants (STD-JD), are used to assess the multi-modality (MM), contour-consistency (CC), and image-intensity (II)-based DIR algorithms in the MIM software package, as well as an in-house developed, contour matching-based finite element method (CM-FEM). Furthermore, we develop a hybrid FEM registration technique to modify the displacement vector field of each MIM registration. The MIM and FEM registrations were evaluated on MRIs obtained from 10 abdominal cancer patients. One-tailed Wilcoxon-Mann-Whitney (WMW) tests were conducted to compare the MIM registrations with their FEM modifications. For the registrations performed with the MIM-CC, MIM-MM, MIM-II, and CM-FEM algorithms, their average MDAs are 0.62±0.27, 2.39±1.30, 3.07±2.42, 1.04±0.72mm, and average DSCs are 0.94±0.03, 0.80±0.12, 0.77±0.15, 0.90±0.11, respectively. The p-values of the WMW tests between the MIM registrations and their FEM modifications are less than 0.0084 for STD-JDs and greater than 0.87 for MDA and DSC. Among the three MIM DIR algorithms, MIM-CC shows the smallest errors in terms of MDA and DSC but exhibits significant Jacobian uncertainties in the interior regions of abdominal organs. The hybrid FEM technique effectively mitigates the Jacobian uncertainties in these regions.

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 > 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 >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 >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 < 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.

Target volumes comparison between postoperative simulation magnetic resonance imaging and preoperative diagnostic magnetic resonance imaging for prone breast radiotherapy after breast-conserving surgery.

This study investigated the differences in target volumes between preoperative magnetic resonance imaging (MRIpre) and postoperative MRI (MRIpost) for breast radiotherapy after breast-conserving surgery (BCS) using deformable image registration (DIR). Seventeen eligible patients who underwent whole-breast irradiation in the prone position after BCS were enrolled. On MRIpre, the gross tumor volume (GTV) was delineated as GTVpre, which was then expanded by 10 mm to represent the preoperative lumpectomy cavity (LC), denoted as LCpre. The LC was expanded to the clinical target volume (CTV) and planning target volume (PTV) on the MRIpre and MRIpost, denoted as CTVpre, CTVpost, PTVpre, and PTVpost, respectively. The MIM software system was used to register the MRIpre and MRIpost using DIR. Differences were evaluated regarding target volume, distance between the centers of mass (dCOM), conformity index (CI), and degree of inclusion (DI). The relationship between CILC /CIPTV and the clinical factors was also assessed. Significant differences were observed in LC and PTV volumes between MRIpre and MRIpost (p < 0.0001). LCpre was 0.85 cm3 larger than LCpost, while PTVpre was 29.38 cm3 smaller than PTVpost. The dCOM between LCpre and LCpost was 1.371 cm, while that between PTVpre and PTVpost reduced to 1.348 cm. There were statistically significant increases in CI and DI for LCpost-LCpre and PTVpost-PTVpre (CI = 0.221, 0.470; DI = 0.472, 0.635). No obvious linear correlations (p > 0.05) were found between CI and GTV, primary tumor volume-to-breast volume ratio, distance from the primary tumor to the nipple and chest wall, and body mass index. Despite using DIR technology, the spatial correspondence of target volumes between MRIpre and MRIpost was suboptimal. Therefore, relying solely on preoperative diagnostic MRI with DIR for postoperative LC delineation is not recommended.

Normal tissue complication probability model of temporal lobe injury following re-irradiation of IMRT for local recurrent nasopharyngeal carcinoma.

We tried to establish the normal tissue complication probability (NTCP) model of temporal lobe injury of recurrent nasopharyngeal carcinoma (NPC) patients after two courses of intensity modulated radiotherapy (IMRT) to provide more reliable dose-volume data reference to set the temporal lobe tolerance dose for recurrent NPC patients in the future. Recurrent NPC patients were randomly divided into training data set and validation data set in a ratio of 2:1, All the temporal lobes (TLs) were re-contoured as R/L structures and named separately in the MIM system. The dose distribution of the initial IMRT plan was deformed into the second course planning CT via MIM software to get the deformed dose. Equivalent dose of TLs in 2Gy fractions was calculated via linear quadratic model, using an α/β=3 for temporal lobes. NTCP model that correlated the irradiated volume of the temporal lobe and? the clinical variables were evaluated in a multivariate prediction model using AUC analysis. From Jan. 2010 to Dec. 2020, 78 patients were enrolled into our study. Among which 26 (33.3%) developed TLI. The most important factors affecting TLI was the sum-dose d1.5cc of TL, while the possible clinical factors did not reach statistically significant differences in multivariate analysis. According to NTCP model, the TD5 and TD50 EQD2 dose of sum-dose d1.5cc were 65.26Gy (46.72-80.69Gy) and 125.25Gy (89.51-152.18Gy), respectively. For the accumulated EQD2 dose, the area under ROC shadow was 0.8702 (0.7577-0.9828) in model validation, p<0.001. In this study, a NTCP model of temporal lobe injury after a second course of IMRT for recurrent nasopharyngeal carcinoma was established. TD5 and TD50 doses of temporal lobe injury after re-RT were obtained according to the model, and the model was verified by validation set data.

Radiomics analysis with three-dimensional and two-dimensional segmentation to predict survival outcomes in pancreatic cancer.

Radiomics can assess prognostic factors in several types of tumors, but considering its prognostic ability in pancreatic cancer has been lacking. To evaluate the performance of two different radiomics software in assessing survival outcomes in pancreatic cancer patients. We retrospectively reviewed pretreatment contrast-enhanced dual-energy computed tomography images from 48 patients with biopsy-confirmed pancreatic ductal adenocarcinoma who later underwent neoadjuvant chemoradiation and surgery. Tumors were segmented using TexRad software for 2-dimensional (2D) analysis and MIM software for 3D analysis, followed by radiomic feature extraction. Cox proportional hazard modeling correlated texture features with overall survival (OS) and progression-free survival (PFS). Cox regression was used to detect differences in OS related to pretreatment tumor size and residual tumor following treatment. The Wilcoxon test was used to show the relationship between tumor volume and the percent of residual tumor. Kaplan-Meier analysis was used to compare survival in patients with different tumor densities in Hounsfield units for both 2D and 3D analysis. 3D analysis showed that higher mean tumor density [hazard ratio (HR) = 0.971, P = 0.041)] and higher median tumor density (HR = 0.970, P = 0.037) correlated with better OS. 2D analysis showed that higher mean tumor density (HR = 0.963, P = 0.014) and higher mean positive pixels (HR = 0.962, P = 0.014) correlated with better OS; higher skewness (HR = 3.067, P = 0.008) and higher kurtosis (HR = 1.176, P = 0.029) correlated with worse OS. Higher entropy correlated with better PFS (HR = 0.056, P = 0.036). Models determined that patients with increased tumor size greater than 1.35 cm were likely to have a higher percentage of residual tumors of over 10%. Several radiomics features can be used as prognostic tools for pancreatic cancer. However, results vary between 2D and 3D analyses. Mean tumor density was the only variable that could reliably predict OS, irrespective of the analysis used.

NIMG-18. MULTI-PARAMETRIC MRI AND SPECT ASSESSMENT OF TREATMENT DOSE AND EFFICACY IN RESPECT-GBM FOR RECURRENT GLIOBLASTOMA (RGBM)

Abstract BACKGROUND We have previously shown a dose-dependent association with survival for patients receiving Rhenium-186-nanoliposome (186RNL) for rGBM. This study aim, applying 3D-dosimetry and advanced-MRI features to outcome assessment, was to extend those findings. METHODS SPECT/CT images were acquired at mid-fusion, end-of-infusion, 24-hour, 120-hour, and 192-hour post-186RNL infusion. Baseline MRI was performed within 7days of treatment, at 28d, and every 56d until progression with: T1-3D pre-/post-contrast agent, DSC, DWI. SPECT images were processed using MIM software with treatment volumes corresponding to the 100Gy isodose curve exported as treatment-ROI. Difference (delta T1) between standardized pre-contrast (T1) and post-contrast (T1_C) anatomic images were used to measure tumor volume (IB Rad Tech). Within the tumor, various MRI-derived parameters, such as standardized-relative-cerebral-blood-volume (srCBV), time to maximum (Tmax), time to peak (TTP), were calculated. RESULTS Perfusion analysis(n=8) revealed significant decreases in the mean nrCBF, nrCBV, rCBF, rCBV, and srCBV with dose [nrCBF: -0.25 95% CI -0.37 to -0.14, p=0.005, nrCBV: -0.23 95% CI -0.34 to -0.13, p=0.005, rCBF: -3.5 95% CI -5.37 to -1.63, p=0.01, rCBV: -11.91 95% CI -20.45 to -3.38, p=0.03, srCBV: -0.14 95% CI -0.23 to -0.05, p=0.02], and a significant increase in the mean Tmax [1.88 95% CI 0.58 to 3.17, p=0.03]. The mean volume (n=10) not covered by treatment (-1.59 95% CI -4.81 to 1.63, p=0.36), Tumor volume (-0.76 95% CI -5.23 to 3.72, p=0.75), Treated volume (3.31 95% CI -0.44 to 7.06, p=0.12), and Tumor Volume covered by treatment (0.84 95% CI -1.2 to 2.87, p=0.44) did not vary significantly with dose although may gain significance with a larger data set. CONCLUSION MRI radiographic features proved valuable in assessing treatment efficacy and guiding treatment considerations. Image processing is ongoing, and the complete data set will be presented.

Early results in the novel use of contrast-enhanced susceptibility-weighted imaging in the assessment of response and progression in desmoid fibromatosis: A pilot study in a specialized cancer institution

Routine radiologic reporting (RRR) often considers progressive desmoid tumors to have a higher proportion of T2-hyperintense and T1-shortened-enhancing components, while responsive or mature collagenized tumors demonstrate a higher proportion of T2-hypointense-non-enhancing components. We aim to determine the utility of the novel use of contrast-enhanced susceptibility-weighted imaging (CE-SWI) in Desmoid-Tumor treatment response assessment, distinguishing between the T1-shortening-enhancing/T2-hyperintense immature components from the T2-hypointense mature collagenized components. This pilot study included 10 single-lesion extremity desmoid fibromatosis patients undergoing standard-of-care magnetic resonance imaging, including CE-SWI. Three-dimensional (3D) tumor segmentation was performed using MIM software in 48 volumes of interest. Maximum diameter, volume, and modified Choi (mChoi) measurements were computed from CE-SWI and T2-weighted image (T2-WI). Five first-order radiomic features, including mean, skewness, kurtosis, and 10th and 90th percentiles, were calculated using in-house developed software (CARPI-AF). (i) RECIST Progression: We observed two cases of progression according to the T2-WI-based Response Evaluation Criteria in Solid Tumors standard (RECIST). Interestingly, CE-SWI-based-volume and CE-SWI-based-mChoi predicted the same assessment 4.5 months earlier than T2-WI-based-RECIST. RRR assessed both cases as progression; (ii) RECIST Stability: Out of the eight patients classified as having stable disease by T2-WI-based-RECIST, four discrepant progressions were determined: three patients showed an increase greater than 25% of T2-WI-based-volume, and two patients showed an increase greater than 25% of CE-SWI-based-volume. Moreover, from the RECIST stable group, four discrepant-positive responses were predicted by CE-SWI-based-mChoi (three patients) and T2-WI-based-mChoi (four patients). RRR only assessed one patient as having progressive disease; (iii) First-Order Radiomics: CE-SWI detected 23% more 90th-percentile voxels than T2-WI, while T2-WI demonstrated 8.5% more 10th-percentile voxels than CE-SWI. Notably, expected first-order response/progression-related changes in 10th-percentile, 90th-percentile, mean, and skewness were present in 90% of cases. In conclusion, CE-SWI-based-volume and CE-SWI-based-mChoi measurements could improve the prediction of response/progression in desmoid tumors, enhancing the ability in discriminating between T2*- hypointense-collagenized-mature and T1-shortened-enhancing immature components, respectively, in predominant mature responsive and immature progressive tumors, respectively. RRR is relatively insensitive to volumetric tumor changes before RECIST progression and tends to be better tuned with T2* signal and enhancement changes.

Abstract 149: Metabolic Neuroimaging in the Assessment of Cardiovascular Risk: A Regional FDG‐PET Analysis

Introduction Emerging evidence suggests a robust association between cardiovascular disease (CVD) and cognitive decline, accentuating the necessity for early detection and intervention. 18F‐fluorodeoxyglucose‐positron emission tomography (FDG‐PET) has proven efficacious in identifying metabolic neurological changes at a molecular level, even before conventional imaging methods can detect structural changes. This study analyzed regional glucose metabolism in individuals with known CVD risk factors. The detection of such metabolic changes could assist in determining the necessity and timing of vascular interventions, such as carotid endarterectomy (CEA) or carotid artery angioplasty with stenting (CAS), contributing to improved patient outcomes and reduced postoperative complications. Methods We compared 79 healthy controls (mean age 44.5 ± 13.8 years, 53.2% males) and 40 individuals (mean age 55.9 ± 11.9 years, 50% males) at increased risk for cardiovascular disease (CVD) as assessed by the systematic coronary risk evaluation tool. All subjects were grouped into two age‐matched cohorts: younger (&lt;45 years) and older (≥45 years). All subjects underwent whole‐body FDG‐PET/CT imaging. The quantitative regional analysis of PET images was performed using MIMneuro version 7.1.5 (MIM Software, Inc., Cleveland, Ohio). 70 neurological structures were analyzed in each subject. An independent samples t‐test was used to assess the differences in z‐scores between controls and at‐risk subjects. The threshold for significance was set at P &lt; 0.05. Results Within the younger cohort, the cingulate gyrus (p=0.0206) and the anterior cingulate gyrus (p=0.0348) demonstrated significant hypometabolism in patients with known cardiac risk factors when compared to healthy controls. Within the older cohort, the supplementary motor area demonstrated significant hypometabolism (p=0.0145), while both the pons (p=0.0169) and pontine tegmentum (p=0.0063) had significant hypermetabolism in patients with known cardiac risk factors when compared to healthy controls. Conclusion Our analysis revealed an inverse relationship between increased cardiovascular disease risk and metabolic activity, particularly in three brain regions: the cingulate gyrus, the anterior cingulate gyrus, and the supplementary motor area. The findings substantiate the vulnerability of the cingulate gyrus to the impacts of small vessel disease. Hypoperfusion, a potential consequence of atherosclerotic plaque accumulation in the perfusing artery, engenders a pernicious cycle of hypoxia, oxidative stress, mitochondrial dysfunction, and inflammation, which exacerbates neuronal cell death. The cingulate gyrus, vascularized by the pericallosal arteries (branches of the anterior cerebral artery from the internal carotid arteries), and the pontine tegmentum, supplied by branches of the basilar artery, are pivotal in this context. Calcification within these arteries could potentially instigate decreased perfusion, thereby contributing to the observed hypometabolism. Examining microstructural and functional changes in the neurovascular system in response to cardiovascular disease risk factors provides key insights. These findings could inform targeted interventions, streamline perioperative strategies, and aid in decision‐making regarding the timing of vascular interventions. Future studies investigating the association among arterial calcification, regional hypometabolism, and cognitive decline may provide a deeper understanding of the complex interplay between cardiovascular health and cognitive function, supporting the improvement of intervention strategies and refinement surgical techniques.

Abstract 152: Exploring Age‐related Changes in Brain Metabolism among Individuals with Cardiovascular Risk Factors: An FDG‐PET Analysis

Introduction Patients with cognitive impairment often have a history of cardiovascular disease (CVD) or multiple cardiovascular risk factors (CRFs) such as hypertension, obesity, and hypercholesterolemia. The literature reports that CVD with CRFs may increase the risk of developing vascular dementia and Alzheimer’s Disease. 18F‐fluorodeoxyglucose positron emission tomography (FDG‐PET) allows for the in vivo study of cerebral glucose metabolism, and can detect metabolic alterations in several neurological diseases. As we age, the brain undergoes both structural and functional changes; the regional distribution of these alterations mirrors cognitive decline. This study aims to assess the effect of aging on regional glucose uptake in subjects with known cardiovascular risk factors. Methods In total, 40 subjects (mean age 55.9 ± 11.89 years, 50% males) with known cardiovascular risk factors underwent FDG‐PET scanning, and 70 whole brain structures were analyzed in each subject. Participants were recruited from a group of patients with chest pain syndromes who were referred for coronary CT angiography. All subjects underwent whole‐body FDG‐PET/CT imaging 180 minutes after the administration of 4.0 MBq/kg dose of FDG. The quantitative regional analysis of PET images was performed using MIMneuro version 7.1.5 (MIM Software, Inc., Cleveland, Ohio). MIMneuro provides region‐based analysis, with z‐scores generated by comparing the patient to the selected age‐matched set of normal controls. Pearson’s R was calculated and evaluated for significance in all variables. The threshold for significance was set at P &lt; 0.05. Results Various significant associations between age and FDG uptake across all 70 brain regions of interest were observed. In particular, age was found to have an inverse correlation with regional metabolism in the middle temporal gyrus (r= ‐0.364, p=0.021), superior frontal gyrus (r= ‐0.433, p=0.005), superior parietal lobule (r= ‐0.354, p=0.025), supplementary motor area (r= ‐0.436, p=0.005), and temporal operculum (r= ‐0.370, p=0.019). Conclusion The results demonstrate a significant inverse correlation between age and FDG uptake in five regions among individuals with cardiovascular risk factors. This information may be useful in the determination of whether such scans might be useful in the evaluation of patients with a history of CVD/CRF or with mild cognitive impairment (MCI). Previous literature has reported that increased medial temporal gyrus atrophy is a predictor of dementia in subjects with MCI, and alterations within this lobe mark the beginning of the disease process. Our strongest inverse correlation, the superior frontal gyrus, has been shown to be related to working memory; hypometabolism in this region has previously correlated with severity of cognitive impairments in attention, executive function, and language. Further research is needed to determine the potential for using FDG‐PET imaging as a tool for early detection and intervention for cognitive decline. If patients with CVD or CRFs can be properly diagnosed, if there exists a metabolic signature of regional functional change, intervention may prove highly beneficial for cognitive function, quality of life, and overall well‐being.

Abstract 015: Pioneering NaF‐PET/CT Imaging for Early Detection of Atherosclerosis: Potential Implications for Neurointerventional Surgery

Introduction Cerebrovascular disease (CVD), particularly carotid artery atherosclerosis, contributes substantially to global morbidity and mortality. The ability to precisely detect atherosclerosis is crucial, as it directly influences patient management, including decisions regarding surgical interventions. Given the high prevalence and severe outcomes of CVD, there is an urgent need for improved early detection methods. Utilizing a novel approach, this study pioneers the use of 18F‐sodium fluoride (NaF) PET/CT imaging for the early identification of microcalcification, a key marker of atherosclerosis. A nuanced understanding of vascular calcification's temporal progression may aid in optimally timing surgical interventions, such as carotid endarterectomy or carotid artery stenting, thereby reducing stroke risk. Methods Our study participant is a 31‐year‐old male with atrial fibrillation, multiple cardiovascular risk factors, and class 2 obesity, enrolled in the Cardiovascular Molecular Calcification Assessed by 18F‐NaF PET/CT (CAMONA) study. The patient underwent both FDG‐PET/CT and NaF‐PET/CT imaging. We utilized OsiriX MD software v.13.0.1 (Pixmeo SARL, Bernex, Switzerland), to compute the standardized uptake value (SUVmean), serving as a measure of disease progression in both the global brain and the bilateral carotid arteries. Subsequently, we employed MIMneuro version 7.1.5 (MIM Software, Inc., Cleveland, OH, USA) to conduct a comprehensive regional brain metabolism analysis, harnessing the power of an integrated anatomical atlas. Results NaF‐PET/CT imaging revealed elevated NaF uptake in the bilateral carotid arteries (z‐score = 0.012), suggesting notable microcalcification. Conversely, FDG‐PET/CT imaging revealed low FDG uptake in the carotid arteries, with an average SUVmean of 0.66 for both right and left carotids and a z‐score of −2.32. Analysis of global brain metabolism demonstrated decreased FDG uptake detected by FDG‐PET/CT (z‐score = ‐2.32). Concurrently, we identified a decline in regional brain metabolism, with prominent decreases observed in regions including the brainstem (z score = −1.95), medial temporal lobe (z‐score = −1.81), cerebellum (z–score = −2.13), hippocampus (z‐score = −2.13), inferior frontal gyrus (z‐score = −3.53), lateral orbital gyrus (z‐score = −3.24), and putamen (z‐score = −2.47) (Figure 1). Conclusion Our findings highlight the potential of NaF‐PET/CT imaging to enhance early detection of carotid artery atherosclerosis and cerebral hypometabolism. These results highlight the subtle, yet potent, potential of NaF‐PET/CT scans to detect active, asymptomatic cases where FDG‐PET/CT scans may not indicate high activity. The findings suggest that NaF‐PET could play a pivotal role in diagnosing and managing CVD where traditional tracers encounter limitations. Early recognition of these alterations facilitates clinical decision‐making, including determining the necessity and timing of surgical intervention. This advanced diagnostic tool presents an opportunity to improve pre‐operative assessments by providing insights into disease progression prior to macrocalcification development, a clear advantage over existing imaging modalities. The correlation between vascular calcification and decreased cerebral metabolism enhances our understanding of CVD pathophysiology, thereby paving the way for transformative therapeutic interventions. While these findings provide preliminary insight, further research is crucial to corroborate our results and delineate their potentially transformative implications on patient care, particularly in the context of surgical interventions.

Abstract 150: Arterial Calcification and Neural Metabolic Activity: Assessing Neurovascular Status Through FDG and NaF PET/CT Imaging

Introduction Atherosclerosis, the occlusion of arteries due to the accumulation of fatty substances, cholesterol, calcium, and fibrin in the arterial walls, can result in reduced blood flow and a subsequent decrease in oxygen delivery to the organs supplied by the affected artery, including the brain. Positron emission tomography‐computed tomography (PET‐CT) utilizing 18F‐fluorodeoxyglucose (FDG) and 18F‐Sodium Fluoride (NaF) have demonstrated efficacy in the assessment of cerebral glucose metabolism and atherosclerotic calcification, respectively. However, the reported literature has not clearly correlated arterial disease throughout the body with cerebral hypometabolism. Utilizing a novel integration of FDG and NaF PET/CT imaging, our study explores the link between cardiovascular risk factors and regional cerebral metabolism. Methods We compared 79 healthy controls (mean age 44.5 ± 13.8 years, 53.2% males) and 40 individuals (mean age 55.9 ± 11.9 years, 50% males) at increased risk for cardiovascular disease (CVD) as assessed by the systematic coronary risk evaluation (SCORE) tool. All subjects underwent whole‐body FDG‐PET/CT imaging. [18F]fluoride PET/CT imaging was performed using hybrid PET/CT scanners with image correction and reconstruction processes following standard protocols. The quantitative regional analysis of PET images was performed using MIMneuro version 7.1.5 (MIM Software, Inc., Cleveland, Ohio). 70 whole brain structures were analyzed in each subject. MIMneuro provided region‐based analysis, with z‐scores generated by comparing the patient to the selected age‐matched set of normal controls. Using OsiriX MD software, [18F]fluoride PET/CT scans were analyzed with regions of interest (ROIs) manually drawn to assess carotid calcification and standardized uptake value mean (SUVmean), along with ROI volume values. Correlations between the degree of molecular calcification and cerebral FDG uptake in patients with cardiovascular risk factors were evaluated using Pearson’s R, with the significance threshold set at P &lt; 0.05. Results Unhealthy patients demonstrated significant negative correlations between increased calcification in the carotid arteries, as assessed by NaF‐PET, and metabolic activity in the anterior cingulate (r = ‐0.42, p = 0.008) and cingulate regions (r = ‐0.34, p = 0.036). Conversely, healthy patients exhibited significant positive correlations in the pons (r = 0.25, p = 0.042) and pontine tegmentum (r = 0.34, p = 0.005), suggestive of a compensatory mechanism to maintain autonomic and motor functions. Conclusion The present study provides insight regarding the interplay between arterial calcification and neural metabolic activity, particularly as it pertains to regions supplied by the anterior cerebral artery. Our investigation suggests that calcification in the carotid arteries, which give rise to the ACA, has a deleterious impact on the function of the cingulate gyrus. Additionally, the observed positive correlation in the pons and pontine tegmentum in healthy individuals raises intriguing questions regarding potential compensatory mechanisms that may help maintain autonomic and motor functions despite vascular impediments. Understanding the temporal progression of vascular calcification allows for the optimization of surgical strategy and timing, potentially reducing stroke risk and improving patient outcomes. These findings underscore the necessity of persistent surveillance and targeted management strategies concerning carotid calcification.

The prognostic value of F18 Fluorothymidine positron emission tomography for assessing the response of malignant pleural mesothelioma to chemotherapy - A prospective cohort study.

Malignant pleural mesothelioma is difficult to prognosticate. F18-Fluorodeoxyglucose positron emission tomography (FDG PET) shows promise for response assessment but is confounded by talc pleurodesis. F18-Fluorothymidine (FLT) PET is an alternative tracer specific for proliferation. We compared the prognostic value of FDG and FLT PET and determined the influence of talc pleurodesis on these parameters. Overall, 29 prospectively recruited patients had FLT PET, FDG PET and CT-scans performed prior to and post one chemotherapy cycle; 10 had prior talc pleurodesis. Patients were followed for overall survival. CT response was assessed using mRECIST. Radiomic features were extracted using the MiM software platform. Changes in maximum SUV (SUVmax), mean SUV (SUVmean), FDG total lesion glycolysis (TLG), FLT total lesion proliferation (TLP) and metabolic tumour volume (MTV) after one chemotherapy cycle. Cox univariate analysis demonstrated FDG PET radiomics were confounded by talc pleurodesis, and that percentage change in FLT MTV was predictive of overall survival. Cox multivariate analysis showed a 10% increase in FLT tumour volume corresponded with 9.5% worsened odds for overall survival (P = 0.028, HR = 1.095, 95% CI [1.010, 1.187]). No other variables were significant on multivariate analysis. This is the first prospective study showing the statistical significance of FLT PET tumour volumes for measuring mesothelioma treatment response. FLT may be better than FDG for monitoring mesothelioma treatment response, which could help optimise mesothelioma treatment regimes.

The implementation of an image-guided system at a proton therapy center facility.

Pencil Beam Scanning (PBS) proton therapy has similar requirements on patient alignment to within 1mm and 1-degree accuracy as photon radiosurgery. This study describes general workflow, acceptance, and commissioning test procedures and their respective results for an independent robotic arm used for Image Guided Radiotherapy (IGRT) for a Proton Therapy System. The system is equipped with kV-imaging techniques capable of orthogonal and Cone-Beam Computed Tomography (CBCT) imaging modalities mounted on an independent robotic arm gantry attached to the ceiling. The imaging system is capable of 360-degree rotation around patients to produce CBCT and kilovoltage orthogonal images. The imaging hardware is controlled by Ehmet Health XIS software, and MIM Software handles the image fusion and registration to an acceptable accuracy of ≤1-mm shifts for patients' alignment. The system was tested according to the requirements outlined in the American Association of Physicists in Medicine (AAPM) Task Group (TG) 142 and TG 179. The system tests included (1) safety, functionality, and connectivity, (2) mechanical testing, (3) image quality, (4) image registration, and (5) imaging dose. Additional tests included imaging gantry isocentricity with a laser tracker and collision-avoiding system checks. The orthogonal and volumetric imaging are comparable in quality to other commercially available On-Board Imagers (OBI) systems. The resulting spatial resolution values were 1.8-, 0.8-, and 0.5-Line Pairs per Millimeter (lp/mm) for orthogonal, full-fan CBCT, and half-fan CBCT, respectively. The image registration is accurate to within 1mm and 1 degree. The data shows consistent imaging-guided system performance with standard deviations in x, y, and z of 0.7, 0.8, and 0.7mm, respectively. The system provides excellent image quality and performance, which can be used for IGRT. The proven accuracy of the x-ray imaging and positioning system at McLaren Proton Therapy Center (MPTC) is 1mm, making it suitable for proton therapy.

Optimal Planning Target Margin for Prostate Radiotherapy Based on Interfractional and Intrafractional Variability Assessment during 1.5T MR-Guided Radiotherapy.

MR-guided radiotherapy (MRgRT) provides superior soft-tissue contrast over CT-based image guidance. We collected and analyzed daily pre-treatment (PRE) and real-time motion-monitoring (MM) MR images of patients receiving prostate radiotherapy to assess interfractional and intrafractional variability of prostate using two localization methods: pelvic bony anatomy (bone) and prostate during online adaptive radiotherapy (ART). PRE and MM MRIs for the first five fractions of twenty prostate cancer patients who received definitive MRgRT with 1.5T MRI were collected. Using MIM software, rigid registration between PRE MRI and planning CT images based on pelvic bony anatomy and prostate reproduced bone localization and online ART, respectively. To determine interfractional setup margin (SM), prostate was delineated on all PRE MRIs registered after bone and prostate localizations by a radiation oncologist, and centroid values of prostate contours between planning CT and PRE MRIs were compared. To determine interobserver variability, another radiation oncologist, a medical physicist, and a radiotherapist contoured prostate for both localization methods. For internal margin (IM) assessment, we used MM MRIs of the five patients who had all three sets of coronal, sagittal, and axial cine images and determined the maximum contour displacement using in-house MATLAB-based software converting binary image files to 2D cine images with a superimposed grid of 1 mm spacing. A total of 100 PRE and 25 MM MRIs were analyzed. Four hundred prostate contours were delineated on MR images registered with planning CT based on both bony anatomy and prostate. After bone localization, SM was 0.57±0.42 mm in left-right (LR), 2.45±1.98 mm in anterior-posterior (AP), and 2.28±2.08 mm in superior-inferior (SI) directions, and IO was 1.06±0.58 mm in LR, 2.32±1.08 mm in AP, and 3.30±1.85 mm in SI directions. After prostate localization, SM was 0.76±0.57 mm in LR, 1.89±1.60 mm in AP, and 2.2±1.79 mm in SI directions, and IO was 1.11±0.55 mm in LR, 2.13±1.07 mm in AP, and 3.53±1.65 mm in SI directions. Average IM was 2.12±0.86 mm, 2.24±1.07 mm, and 2.84±0.88 mm in LR, AP, and SI directions, respectively. Using daily MRIs from MRgRT, we showed that movements in the SI direction were the largest source of variability in prostate definitive RT. In addition, interobserver variability was a non-negligible source of margin. Optimal PTV margin should also consider internal margin, especially in the SI direction.

P05.02.A PRELIMINARY FINDINGS FROM THE MRI QUALITY ASSURANCE PROGRAMME FOR THE PROSPECTIVE MULTI-SITE AUSTRALIAN FIG ([FET-PET IN GLIOBLASTOMA) TROG 18.06 STUDY

Abstract BACKGROUND The O-(2-[18F]-fluoroethyl)-L-tyrosine positron emission tomography (FET-PET) in Glioblastoma (FIG) study is a prospective study evaluating the management impact of FET-PET imaging in up to 210 newly diagnosed adult glioblastoma patients across 10 Australian sites. Patients undergo contrast MRI and FET-PET at 3 timepoints: pre-chemoradiotherapy (CRT), one-month post-CRT and at suspected progression. MRI QA programme components, approach and integrated workflows are described here. MATERIAL AND METHODS The FIG MRI protocol comprised 3D-T1, 3D-FLAIR, Axial 2D DWI (including derived ADC map), DCE (including T1 mapping), DSC, Axial T2 and 3D T1-post-contrast (T1C) sequences, with SWI and 3D DIR sequences optional. QA components included data acquisition quality and completeness (standard and advanced), motion artefact, low contrast to noise or signal to noise, series description and susceptibility artifacts. Suitability of T1/T1C using modified RANO (mRANO) criteria was assessed. An optimised workflow involved site upload from local PACS systems to centralised database via TROG Central Quality Management System (CQMS) platform and collation into a central imaging database utilising MIM software. The MRI QA workflow encompassed automated anonymisation of DICOM data, data completeness and reconstruction evaluation, then review by two expert neuroimaging analysts. Sites received feedback with request for resubmission where required. RESULTS Between December 2021 and February 2023, MRI data in 74 patients across 9 sites with median of 6 patients (range 2-17) per site was submitted. A total of 141 MRI datasets across all timepoints were collected (per site range:4-35, median:13), with 43 imaging time-points selected for QA (per site range:3-12, median: 4). Importantly, 41/43 (95%) of initial datasets were deemed suitable for mRANO assessment, but only 13/43 (30%) were suitable for advanced MRI analysis. Very few datasets had motion or susceptibility artifacts, low contrast to noise or signal to noise, or incorrect series description. Technical issues identified included incomplete data (DCE - missing T1 maps, DWI - missing ADC maps), incorrect sequence reconstruction (DCE split series and Axial/Sagittal/Coronal reformats for 3D images) and lack of non-mandatory SWI sequences. Feedback to sites resulted in improvements in DCE sequence acquisition from split series in 11/45 (24%) to preferred single series in 18/24 (75%) and similar increases in T1 maps completeness from 7/19 (37%) to 7/7 (100%). CONCLUSION Despite challenges in multisite workflow and substantial multi-modality site and central data management, a robust MRI QA program has confirmed 95% compliance for mRANO assessment. Site specific feedback resulted in increased compliance with advanced MRI sequences to enable detailed future analysis.