PET-MRI Research Articles

The Image Biomarker Standardization Initiative: Standardized Convolutional Filters for Reproducible Radiomics and Enhanced Clinical Insights.

Filters are commonly used to enhance specific structures and patterns in images, such as vessels or peritumoral regions, to enable clinical insights beyond the visible image using radiomics. However, their lack of standardization restricts reproducibility and clinical translation of radiomics decision support tools. In this special report, teams of researchers who developed radiomics software participated in a three-phase study (September 2020 to December 2022) to establish a standardized set of filters. The first two phases focused on finding reference filtered images and reference feature values for commonly used convolutional filters: mean, Laplacian of Gaussian, Laws and Gabor kernels, separable and nonseparable wavelets (including decomposed forms), and Riesz transformations. In the first phase, 15 teams used digital phantoms to establish 33 reference filtered images of 36 filter configurations. In phase 2, 11 teams used a chest CT image to derive reference values for 323 of 396 features computed from filtered images using 22 filter and image processing configurations. Reference filtered images and feature values for Riesz transformations were not established. Reproducibility of standardized convolutional filters was validated on a public data set of multimodal imaging (CT, fluorodeoxyglucose PET, and T1-weighted MRI) in 51 patients with soft-tissue sarcoma. At validation, reproducibility of 486 features computed from filtered images using nine configurations × three imaging modalities was assessed using the lower bounds of 95% CIs of intraclass correlation coefficients. Out of 486 features, 458 were found to be reproducible across nine teams with lower bounds of 95% CIs of intraclass correlation coefficients greater than 0.75. In conclusion, eight filter types were standardized with reference filtered images and reference feature values for verifying and calibrating radiomics software packages. A web-based tool is available for compliance checking.

PET imaging of unruptured intracranial aneurysm inflammation (PET-IA) study: a feasibility study protocol

IntroductionPositron emission tomography (PET) imaging can be used to evaluate arterial wall inflammation in extracranial vascular diseases. However, the application of PET imaging in unruptured intracranial aneurysms (UIA) remains unexplored....

18F-FACBC and 18F-FDG PET/MRI in the evaluation of 3 patients with primary central nervous system lymphoma: a pilot study

BackgroundThis PET/MRI study compared contrast-enhanced MRI, 18F-FACBC-, and 18F-FDG-PET in the detection of primary central nervous system lymphomas (PCNSL) in patients before and after high-dose methotrexate chemotherapy. Three immunocompetent PCNSL patients with diffuse large B-cell lymphoma received dynamic 18F-FACBC- and 18F-FDG-PET/MRI at baseline and response assessment. Lesion detection was defined by clinical evaluation of contrast enhanced T1 MRI (ce-MRI) and visual PET tracer uptake. SUVs and tumor-to-background ratios (TBRs) (for 18F-FACBC and 18F-FDG) and time-activity curves (for 18F-FACBC) were assessed.ResultsAt baseline, seven ce-MRI detected lesions were also detected with 18F-FACBC with high SUVs and TBRs (SUVmax:mean, 4.73, TBRmax: mean, 9.32, SUVpeak: mean, 3.21, TBRpeak:mean: 6.30). High TBR values of 18F-FACBC detected lesions were attributed to low SUVbackground. Baseline 18F-FDG detected six lesions with high SUVs (SUVmax: mean, 13.88). In response scans, two lesions were detected with ce-MRI, while only one was detected with 18F-FACBC. The lesion not detected with 18F-FACBC was a small atypical MRI detected lesion, which may indicate no residual disease, as this patient was still in complete remission 12 months after initial diagnosis. No lesions were detected with 18F-FDG in the response scans.Conclusions18F-FACBC provided high tumor contrast, outperforming 18F-FDG in lesion detection at both baseline and in response assessment. 18F-FACBC may be a useful supplement to ce-MRI in PCNSL detection and response assessment, but further studies are required to validate these findings.Trial registration ClinicalTrials.gov. Registered 15th of June 2017 (Identifier: NCT03188354, https://clinicaltrials.gov/study/NCT03188354).

Comparison of 18F-FDG PET and arterial spin labeling MRI in evaluating Alzheimer’s disease and amnestic mild cognitive impairment using integrated PET/MR

BackgroundDeveloping biomarkers for early stage AD patients is crucial. Glucose metabolism measured by 18F-FDG PET is the most common biomarker for evaluating cellular energy metabolism to diagnose AD. Arterial spin labeling (ASL) MRI can potentially provide comparable diagnostic information to 18F-FDG PET in patients with neurodegenerative disorders. However, the conclusions about the diagnostic performance of AD are still controversial between 18F-FDG PET and ASL. This study aims to compare quantitative cerebral blood flow (CBF) and glucose metabolism measured by 18F-FDG PET diagnostic values in patients with Alzheimer’s disease (AD) and amnestic mild cognitive impairment (aMCI) using integrated PET/MR.ResultsAnalyses revealed overlapping between decreased regional rCBF and 18F-FDG PET SUVR in patients with AD compared with NC participants in the bilateral parietotemporal regions, frontal cortex, and cingulate cortex. Compared with NC participants, patients with aMCI exclusively demonstrated lower 18F-FDG PET SUVR in the bilateral temporal cortex, insula cortex, and inferior frontal cortex. Comparison of the rCBF in patients with aMCI and NC participants revealed no significant difference (P > 0.05). The ROC analysis of rCBF in the meta-ROI could diagnose patients with AD (AUC, 0.87) but not aMCI (AUC, 0.61). The specificity of diagnosing aMCI has been improved to 75.56% when combining rCBF and 18F-FDG PET SUVR.ConclusionASL could detect similar aberrant patterns of abnormalities compared to 18F-FDG PET in patients with AD compared with NC participants but not in aMCI. The diagnostic efficiency of 18F-FDG-PET for AD and aMCI patients remained higher to ASL. Our findings support that applying 18F-FDG PET may be preferable for diagnosing AD and aMCI.

18F-ASEM PET/MRI targeting alpha7-nicotinic acetylcholine receptor can reveal skeletal muscle denervation

BackgroundThe increased expression of the nicotinic acetylcholine receptor (nAChR) in muscle denervation is thought to be associated with electrophysiological acetylcholine supersensitivity after nerve injury. Hence, we investigated the utility of the 18F-ASEM alpha7-nAChR targeting radiotracer as a new diagnostic method by visualizing skeletal muscle denervation in mouse models of sciatic nerve injury.MethodsTen-week-old C57BL/6 male mice were utilized. The mice were anesthetized, and the left sciatic nerve was resected after splitting the gluteal muscle. One week (n = 11) and three weeks (n = 6) after the denervation, 18F-ASEM positron emission tomography/magnetic resonance imaging (PET/MRI) was acquired. Maximum standardized uptake values (SUVmax) of the tibialis anterior muscle were measured for the denervated side and the control side. Autoradiographic evaluation was performed to measure the mean counts of the denervated and control tibialis anterior muscles at one week. In addition, immunohistochemistry was used to identify alpha7-nAChR-positive areas in denervated and control tibialis anterior muscles at one week (n = 6). Furthermore, a blocking study was conducted with methyllycaconitine (MLA, n = 5).Results18F-ASEM PET/MRI showed significantly increased 18F-ASEM uptake in the denervated tibialis anterior muscle relative to the control side one week and three weeks post-denervation. SUVmax of the denervated muscles at one week and three weeks showed significantly higher uptake than the control (P = 0.0033 and 0.0277, respectively). The relative uptake by autoradiography for the denervated muscle was significantly higher than in the control, and immunohistochemistry revealed significantly greater alpha7-nAChR expression in the denervated muscle (P = 0.0277). In addition, the blocking study showed no significant 18F-ASEM uptake in the denervated side when compared to the control (P = 0.0796).ConclusionsOur results suggest that nAChR imaging with 18F-ASEM has potential as a noninvasive diagnostic method for peripheral nervous system disorders.

Using multiparametric Magnetic Resonance Imaging and Prostate Specific Membrane Antigen Positron Emission Tomography to detect and delineate the gross tumour volume of intraprostatic lesions – A systematic review and meta-analysis

Background and PurposeRadiation therapy is used frequently for patients with prostate cancer. Dose escalation to intraprostatic lesions (IPLs) has been shown to improve oncologic outcomes, without increasing toxicity. Both multiparametric MRI (mpMRI) and PSMA PET can be used to identify IPLs. Materials and MethodsA systematic review was conducted to determine the ability of mpMRI, PSMA PET and their combination to detect IPLs prior to radical prostatectomy (RP) as correlated with the histology. Trials included patients that had mpMRI, PSMA PET, or both, prior to RP. The quality of the histopathological-radiological co-registration was assessed as high or low for each study. Recorded outcomes include sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC). A meta-analysis was conducted using a bivariate model to determine the pooled sensitivity and specificity for each imaging modality. This systematic review was registered through PROSPERO (CRD42023389092). ResultsAltogether, 42 studies were included in the systematic review. Of these, 20 could be included in the meta-analysis. The pooled sensitivity (95 % CI), specificity (95 % CI) and AUROC for mpMRI (n = 13 studies) were 64.7 % (50.2 % – 76.9 %), 86.4 % (79.7 % − 91.1 %), and 0.852; the pooled outcomes for PSMA PET (n = 12) were 75.7 % (64.0 % − 84.5 %), 87.1 % (80.2 % − 91.9 %), and 0.889; for their combination (n = 5), the pooled outcomes were 70.3 % (64.1 % − 75.9 %), 81.9 % (71.9 % − 88.8 %), and 0.796. When reviewing studies with a high-quality histopathological-radiological co-registration, IPL delineation recommendations varied by study and the imaging modality used. ConclusionAll of mpMRI, PSMA PET or their combination were found to have very good diagnostic outcomes for detecting IPLs. Recommendations for delineating IPLs varied based on the imaging modalities used and between research groups. Consensus guidelines for IPL delineation would help with creating consistency for focal boost radiation treatments in future studies.

Amino acid PET vs. RANO MRI for prediction of overall survival in patients with recurrent high grade glioma under bevacizumab therapy.

To summarize evidence on the comparative value of amino acid (AA) PET and conventional MRI for prediction of overall survival (OS) in patients with recurrent high grade glioma (rHGG) under bevacizumab therapy. Medical databases were screened for studies with individual data on OS, follow-up MRI, and PET findings in the same patient. MRI images were assessed according to the RANO criteria. A receiver operating characteristic curve analysis was used to predict OS at 9 months. Five studies with a total of 72 patients were included. Median OS was significantly lower in the PET-positive than in the PET-negative group. PET findings predicted OS with a pooled sensitivity and specificity of 76% and 71%, respectively. Corresponding values for MRI were 32% and 82%. Area under the curve and sensitivity were significantly higher for PET than for MRI. For monitoring of patients with rHGG under bevacizumab therapy, AA-PET should be preferred over RANO MRI.

Abstract A036: Quantitative molecular imaging of pancreatic tumor fibrosis for evaluation of response to neoadjuvant therapy: Pre-clinical and first-in-human application of collagen PET/MRI

Abstract Purpose: One of the major challenges in the management of pancreatic ductal adenocarcinoma (PDAC) is the lack of a reliable imaging tool to monitor tumor response to treatment. A high degree of fibrosis, mainly collagen type I, has been recognized as the hallmark of PDAC, which further increases in response to neoadjuvant chemoradiotherapy (CRT). This study introduces an image-guided paradigm for monitoring treatment response using the collagen type I specific PET imaging probe, 68Ga-CBP8 in mouse models and patients with PDAC. Methods: Subcutaneous mouse models of human PDAC were generated using FOLFIRNOX-sensitive (PANC1 and PDAC6) and FOLFIRINOX-resistant (SU8686) PDAC cells in nude mice (n=88). Mice were randomized into 2 groups of treatment with FOLFIRINOX or vehicle i.v. twice a week. Animals underwent PET/MRI with 68Ga-CBP8 (3.7-11.1 MBq) prior to, and at 7- and 15-days post-treatment (n=4-8/group). To assess the specificity of the probe, additional PANC1 tumor-bearing mice (n=4) were imaged with 68Ga-CBP8, and a collagen non-binding probe, 68Ga-CNBP (3.7-11 MBq). PET values were correlated with tumor growth over 21 days and quantification of fibrosis by Picrosirius red and IHC for collagen I, α-SMA, FAP-α, collagen rtPCR, and hydroxyproline assay. 8 patients (49-65 yrs.) with newly diagnosed PDAC underwent 68Ga-CBP8 PET (122-281 MBq) and standard MRI. Thus far, 3/8 subjects have undergone repeat PET/MRI after completion of neoadjuvant CRT. The pre-and post-CRT PET parameters for tumor and pancreas were compared and correlated with tumor size change, histology, and spatial analyses for PDAC and fibroblasts. Results: PET/MRI of PANC1 tumors showed significantly higher 68Ga-CBP8 uptake compared to control 68Ga-CNBP at each time point (p < 0.05), demonstrating the specificity of the probe in targeting collagen. PET values significantly increased over time in FOLFIRINOX-sensitive tumors (PANC1 %ID/cc: 0.8 ± 0.2 vs. 1.1 ± 0.3 vs. 1.9 ±0.2, p < 0.05 in day-0 vs. day-7 vs. day-15, respectively, p = 0.0005), whereas no significant change was seen in the probe uptake in the vehicle or resistant tumors (p > 0.05). There was a significant tumor growth reduction in responders compared to vehicle and resistant tumors. Histology showed a continuous increase of collagen in responding tumors (% collagen proportion area (CPA) in PANC1: 5.2 ± 3.8 vs. 16.2 ± 8.7 vs. 46.9 ± 6.0, p < 0.05, at Day-0 vs. Day-7 vs. Day-15, respectively, p < 0.0001), no change in resistant SU8686 (CPA: 33.0 ± 8.9 vs. 30.0 ± 9.7 vs. 28.1 ± 7.2, at Day-0 vs. Day-7 vs. Day-15, respectively, p = 0.66) and unchanged minimal collagen in pancreas. PET/MRI of patients showed a significantly higher SUVmean in the tumor compared to pancreas (2.4 ± 0.37 vs. 1.9 ± 0.31, p = 0.01), and a significantly higher uptake in the treated compared to untreated tumors (SUVmean: 2.8 ± 0.33 vs. 1.9 ± 0.56, p = 0.04). Response to treatment was confirmed on histology. Conclusion: Collagen PET could be used as a reliable non-invasive tool for monitoring response to neoadjuvant therapy in PDAC. Citation Format: Shadi A. Esfahani, Hua Ma, Shriya Krishna, Sergey Shuvaev, Arvin Hajmirzaian, Iris Zhou, Ciprian Catana, Mozhdeh Sojoodi, Eric Abston, David Ting, Pedram Heidari, Michael Lanuti, Kenneth Tanabe, Motaz Qadan, Carlos Fernandez de-Castillo, Aparna Parikh, Colin Weekes, Theodore Hong, Peter Caravan. Quantitative molecular imaging of pancreatic tumor fibrosis for evaluation of response to neoadjuvant therapy: Pre-clinical and first-in-human application of collagen PET/MRI [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr A036.

Non-rigid motion-compensated 3D whole-heart T2 mapping in a hybrid 3T PET-MR system.

Simultaneous PET-MRI improves inflammatory cardiac disease diagnosis. However, challenges persist in respiratory motion and mis-registration between free-breathing 3D PET and 2D breath-held MR images. We propose a free-breathing non-rigid motion-compensated 3D T2 -mapping sequence enabling whole-heart myocardial tissue characterization in a hybrid 3T PET-MR system and provides non-rigid respiratory motion fields to correct also simultaneously acquired PET data. Free-breathing 3D whole-heart T2 -mapping was implemented on a hybrid 3T PET-MRI system. Three datasets were acquired with different T2 -preparation modules (0, 28, 55 ms) using 3-fold undersampled variable-density Cartesian trajectory. Respiratory motion was estimated via virtual 3D image navigators, enabling multi-contrast non-rigid motion-corrected MR reconstruction. T2 -maps were computed using dictionary-matching. Approach was tested in phantom, 8 healthy subjects, 14 MR only and 2 PET-MR patients with suspected cardiac disease and compared with spin echo reference (phantom) and clinical 2D T2 -mapping (in-vivo). Phantom results show a high correlation (R2 = 0.996) between proposed approach and gold standard 2D T2 mapping. In-vivo 3D T2 -mapping average values in healthy subjects (39.0 ± 1.4 ms) and patients (healthy tissue) (39.1 ± 1.4 ms) agree with conventional 2D T2 -mapping (healthy = 38.6 ± 1.2 ms, patients = 40.3 ± 1.7 ms). Bland-Altman analysis reveals bias of 1.8 ms and 95% limits of agreement (LOA) of -2.4-6 ms for healthy subjects, and bias of 1.3 ms and 95% LOA of -1.9 to 4.6 ms for patients. Validated efficient 3D whole-heart T2 -mapping at hybrid 3T PET-MRI provides myocardial inflammation characterization and non-rigid respiratory motion fields for simultaneous PET data correction. Comparable T2 values were achieved with both 3D and 2D methods. Improved image quality was observed in the PET images after MR-based motion correction.

Direct comparison between 18F-Flortaucipir tau PET and quantitative susceptibility mapping in progressive supranuclear palsy

PurposeThe pattern of flortaucipir tau PET uptake is topographically similar to the pattern of magnetic susceptibility in progressive supranuclear palsy (PSP); both with increased signal in subcortical structures such as the basal ganglia and midbrain, suggesting that they may be closely related. However, their relationship remains unknown since no studies have directly compared these two modalities in the same PSP cohort. We hypothesized that some flortaucipir uptake in PSP is associated with magnetic susceptibility, and hence iron deposition. The aim of this study was to evaluate the regional relationship between flortaucipir uptake and magnetic susceptibility and to examine the effects of susceptibility on flortaucipir uptake in PSP. MethodsFifty PSP patients and 67 cognitively normal controls were prospectively recruited and underwent three Tesla MRI and flortaucipir tau PET scans. Quantitative susceptibility maps were reconstructed from multi-echo gradient-echo MRI images. Region of interest (ROI) analysis was performed to obtain flortaucipir and susceptibility values in the subcortical regions. Relationships between flortaucipir and susceptibility signals were evaluated using partial correlation analysis in the subcortical ROIs and voxel-based analysis in the whole brain. The effects of susceptibility on flortaucipir uptake were examined by using the framework of mediation analysis. ResultsBoth flortaucipir and susceptibility were greater in PSP compared to controls in the putamen, pallidum, subthalamic nucleus, red nucleus, and cerebellar dentate (p<0.05). The ROI-based and voxel-based analyses showed that these two signals were positively correlated in these five regions (r = 0.36–0.59, p<0.05). Mediation analysis showed that greater flortaucipir uptake was partially explained by susceptibility in the putamen, pallidum, subthalamic nucleus, and red nucleus, and fully explained in the cerebellar dentate. ConclusionsThese results suggest that some of the flortaucipir uptake in subcortical regions in PSP is related to iron deposition. These findings will contribute to our understanding of the mechanisms underlying flortaucipir tau PET findings in PSP and other neurodegenerative diseases.

The mediating effect of 18F-FDG metabolism in right caudate between depressive symptoms and cognitive function in Alzheimer's disease.

The objective of this study was to investigate the accumulation of 18F-fluorodeoxyglucose (18F-FDG) in the whole brain between Alzheimer's disease (AD) with depressive (ADD) symptoms compared with AD without depressive (ADND) symptoms using positron emission tomography/magnetic resonance imaging (PET/MRI). Additionally, this study aimed to explore the associations among the accumulation of 18F-FDG in the brain, depressive symptoms, and cognitive function in ADD patients. In this study, 25 AD patients and 22 healthy controls were enrolled. The AD patients were stratified into two groups, namely ADD and ADND, based on their scores of the Hamilton Depression Scale (HAMD). Both AD patients and healthy controls underwent an 18F-FDG PET/MRI scan. A standardized uptake value ratio (SUVR) was calculated to examine the accumulation of 18F-FDG in the brain. A simple mediation model was employed to examine the mediation effect between SUVR, depressive symptoms and cognitive function in ADD patients. The ADD group exhibited significant cognitive impairment compared to the ADND group (p < 0.001) and healthy controls (p < 0.001). The ADD patients exhibited the reduced SUVR (0.228 ± 0.126) in the right caudate (the voxel level p < 0.005, cluster level p < 0.05, after false discovery rate (FDR) correction) compared to ADND patients (0.459 ± 0.064) and healthy controls (0.706 ± 0.122). The SUVR of the right caudate was correlated with the HAMD scores (r = -0.792, p < 0.001) and mini-mental state examination (MMSE) (r = 0.738, p < 0.01). The relationship between depressive symptoms and the cognitive function in ADD patients is mediated by the right caudate SUVR (total effects = -0.385, direct effects = -0.02, total indirect effects = -0.405). The ADD group exhibited the reduced SUVR in the right caudate compared to the ADND group and healthy controls. The relationship between depressive symptoms and the cognitive ability of AD patients was mediated by the right caudate SUVR. The results contribute to a deeper understanding of the neurobiological mechanisms related to AD with depressive symptoms.

Alzheimer Disease Pathology and Neurodegeneration in Midlife Obesity: A Pilot Study.

Obesity and excess adiposity at midlife are risk factors for Alzheimer disease (AD). Visceral fat is known to be associated with insulin resistance and a pro-inflammatory state, the two mechanisms involved in AD pathology. We assessed the association of obesity, MRI-determined abdominal adipose tissue volumes, and insulin resistance with PET-determined amyloid and tau uptake in default mode network areas, and MRI-determined brain volume and cortical thickness in AD cortical signature in the cognitively normal midlife population. Thirty-two middle-aged (age: 51.27±6.12 years, 15 males, body mass index (BMI): 32.28±6.39 kg/m2) cognitively normal participants, underwent bloodwork, brain and abdominal MRI, and amyloid and tau PET scan. Visceral and subcutaneous adipose tissue (VAT, SAT) were semi-automatically segmented using VOXel Analysis Suite (Voxa). FreeSurfer was used to automatically segment brain regions using a probabilistic atlas. PET scans were acquired using [11C]PiB and AV-1451 tracers and were analyzed using PET unified pipeline. The association of brain volumes, cortical thicknesses, and PiB and AV-1451 standardized uptake value ratios (SUVRs) with BMI, VAT/SAT ratio, and insulin resistance were assessed using Spearman's partial correlation. VAT/SAT ratio was associated significantly with PiB SUVRs in the right precuneus cortex (p=0.034) overall, controlling for sex. This association was significant only in males (p=0.044), not females (p=0.166). Higher VAT/SAT ratio and PiB SUVRs in the right precuneus cortex were associated with lower cortical thickness in AD-signature areas predominantly including bilateral temporal cortices, parahippocampal, medial orbitofrontal, and cingulate cortices, with age and sex as covariates. Also, higher BMI and insulin resistance were associated with lower cortical thickness in bilateral temporal poles. In midlife cognitively normal adults, we demonstrated higher amyloid pathology in the right precuneus cortex in individuals with a higher VAT/SAT ratio, a marker of visceral obesity, along with a lower cortical thickness in AD-signature areas associated with higher visceral obesity, insulin resistance, and amyloid pathology.

Neuroimmune activation and increased brain aging in chronic pain patients after the COVID-19 pandemic onset

The COVID-19 pandemic has exerted a global impact on both physical and mental health, and clinical populations have been disproportionally affected. To date, however, the mechanisms underlying the deleterious effects of the pandemic on pre-existing clinical conditions remain unclear. Here we investigated whether the onset of the pandemic was associated with an increase in brain/blood levels of inflammatory markers and MRI-estimated brain age in patients with chronic low back pain (cLBP), irrespective of their infection history. A retrospective cohort study was conducted on 56 adult participants with cLBP (28 ‘Pre-Pandemic’, 28 ‘Pandemic’) using integrated Positron Emission Tomography/ Magnetic Resonance Imaging (PET/MRI) and the radioligand [11C]PBR28, which binds to the neuroinflammatory marker 18 kDa Translocator Protein (TSPO). Image data were collected between November 2017 and January 2020 (‘Pre-Pandemic’ cLBP) or between August 2020 and May 2022 (‘Pandemic’ cLBP). Compared to the Pre-Pandemic group, the Pandemic patients demonstrated widespread and statistically significant elevations in brain TSPO levels (P =.05, cluster corrected). PET signal elevations in the Pandemic group were also observed when 1) excluding 3 Pandemic subjects with a known history of COVID infection, or 2) using secondary outcome measures (volume of distribution -VT- and VT ratio - DVR) in a smaller subset of participants. Pandemic subjects also exhibited elevated serum levels of inflammatory markers (IL-16; P <.05) and estimated BA (P <.0001), which were positively correlated with [11C]PBR28 SUVR (r’s ≥ 0.35; P’s < 0.05). The pain interference scores, which were elevated in the Pandemic group (P <.05), were negatively correlated with [11C]PBR28 SUVR in the amygdala (r = −0.46; P<.05).This work suggests that the pandemic outbreak may have been accompanied by neuroinflammation and increased brain age in cLBP patients, as measured by multimodal imaging and serum testing. This study underscores the broad impact of the pandemic on human health, which extends beyond the morbidity solely mediated by the virus itself.

Systematic evaluation of human soft tissue attenuation correction in whole-body PET/MR: Implications from PET/CT for optimization of MR-based AC in patients with normal lung tissue.

Attenuation correction (AC) is an important methodical step in positron emission tomography/magnetic resonance imaging (PET/MRI) to correct for attenuated and scattered PET photons. The overall quality of magnetic resonance (MR)-based AC in whole-body PET/MRI was evaluated in direct comparison to computed tomography (CT)-based AC serving as reference. The quantitative impact of isolated tissue classes in the MR-AC was systematically investigated to identify potential optimization needs and strategies. Data of n=60 whole-body PET/CT patients with normal lung tissue and without metal implants/prostheses were used to generate six different AC-models based on the CT data for each patient, simulating variations of MR-AC. The original continuous CT-AC (CT-org) is referred to as reference. A pseudo MR-AC (CT-mrac), generated from CT data, with four tissue classes and a bone atlas represents the MR-AC. Relative difference in linear attenuation coefficients (LAC) and standardized uptake values were calculated. From the results two improvements regarding soft tissue AC and lung AC were proposed and evaluated. The overall performance of MR-AC is in good agreement compared to CT-AC. Lungs, heart, and bone tissue were identified as the regions with most deviation to the CT-AC (myocardium -15%, bone tissue -14%, and lungs ±20%). Using single-valued LACs for AC in the lung only provides limited accuracy. For improved soft tissue AC, splitting the combined soft tissue class into muscles and organs each with adapted LAC could reduce the deviations to the CT-AC to <±1%. For improved lung AC, applying a gradient LAC in the lungs could remarkably reduce over- or undercorrections in PET signal compared to CT-AC (±5%). The AC is important to ensure best PET image quality and accurate PET quantification for diagnostics and radiotherapy planning. The optimized segment-based AC proposed in this study, which was evaluated on PET/CT data, inherently reduces quantification bias in normal lung tissue and soft tissue compared to the CT-AC reference.

Diagnosis of Hepatic Alveolar Echinococcosis with Massive Peritoneal Seeding Treated Surgically- A Case Report

The diagnosis of Alveolar Echinococcosis is often a difficult diagnosis due to its low incidence and a long asymptomatic incubation period. We report a case of a 32-year-old man with an uncommon location of Alveolar Echinococcosis. He presented abdominal pain, conjunctival icterus and dark urine. Abdominal ultrasonography, CT scan and MRI demonstrated the presence of a hepatic lesion and a pararectal mass associated with peritoneal and omental implants. The lesions showed perilesional hypermetabolism on 18F-fluorodeoxiglucose (FDG) positron emission tomography magnetic resonance imaging (PET/MRI). Para-rectal biopsy, serological test, and sample taken during exploratory laparoscopy all suggested Echinococcus multilocularis infection that was later confirmed by PCR test. The patient was treated with Albendazole and underwent curative-intent twostep surgery by right-extended hepatectomy, resection of all peritoneal implants and total mesorectal excision. Thirty months after initial surgery, the patient is doing well and is followed up with MRI and 18F-FDG-PET without morphological signs of recurrence. This case illustrates the capacity of alveolar echinococcosis to affect different organs by infiltration or metastatic dissemination and highlights the role of 18F-FDG-PET/MRI in diagnosis and disease monitoring.

Multimodal MRI and tau PET findings from the Autosomal Dominant Alzheimer’s disease cohort caused by the A431E PSEN1 Jalisco mutation

AbstractBackgroundThe A431E mutation in PSEN1 is a cause of Autosomal Dominant Alzheimer’s disease (ADAD) that represents a founder effect, apparently arising from the state of Jalisco, Mexico, with over 100 superficially distinct families being affected. The median age of symptom onset is 41 years, with about 40% of cases having an atypical presentation of substantial spastic paraparesis. This study aimed to identify the neuroimaging features associated with the A431E PSEN1 Jalisco mutation to elucidate its pathophysiology and to inform future clinical studies.MethodThirty‐one participants with or known to be at‐risk for the A431E PSEN1 mutation were enrolled in a comprehensive genetic, clinical, and imaging protocol including MRI and flortaucipir PET scans. Diffusion MRI and flortaucipir PET studies were conducted on sub‐samples of the cohort along with appropriate control participants.ResultPeak flortaucipir standard uptake value ratio (SUVR) among A431E mutation carriers was predominantly in the lateral parietal cortices relative to the medial temporal lobes with disproportionate signal in motor and sensory cortex relative to persons with late onset AD. Flortaucipir SUVR in 6 brain regions (i.e., medial orbitofrontal, caudal and rostral anterior cingulate, parahippocampal, precuneus, and lateral occipital) were associated with neuropsychiatric symptoms in persons with or at risk for the A431E PSEN1 mutation. Among 21 A431E PSEN1 mutation carriers with available diffusion MRI images, the Ashworth score of spastic paraparesis correlated with mean diffusivity in several brain regions, particularly left inferior parietal, superior parietal, and paracentral lobules (r’s&gt;0.8, p’s&lt; 0.001). In a subset of 10 clinically impaired A431E PSEN1 mutation carriers, mean diffusivity in white matter tracts underlying multiple cortical areas was higher relative to 8 impaired persons with late onset AD or ADAD mutations that do not cause spastic paraparesis.ConclusionThe pattern of flortaucipir distribution was atypical with disproportionate involvement of sensorimotor areas and parietal cortex. Higher flortaucipir signal was associated with more neuropsychiatric symptoms. Microstructural changes in white matter were more pronounced in persons with the A431E PSEN1 mutation and likely underlie the associated spastic paraparesis. The distinct neuroimaging features and associated neuropsychiatric manifestations observed in this cohort highlight the importance of comprehensively characterizing heterogeneous AD subtypes.

Multimodal MRI and tau PET findings from the Autosomal Dominant Alzheimer’s disease cohort caused by the A431E PSEN1 Jalisco mutation

AbstractBackgroundThe A431E mutation in PSEN1 is a cause of Autosomal Dominant Alzheimer’s disease (ADAD) that represents a founder effect, apparently arising from the state of Jalisco, Mexico, with over 100 superficially distinct families being affected. The median age of symptom onset is 41 years, with about 40% of cases having an atypical presentation of substantial spastic paraparesis. This study aimed to identify the neuroimaging features associated with the A431E PSEN1 Jalisco mutation to elucidate its pathophysiology and to inform future clinical studies.MethodThirty‐one participants with or known to be at‐risk for the A431E PSEN1 mutation were enrolled in a comprehensive genetic, clinical, and imaging protocol including MRI and flortaucipir PET scans. Diffusion MRI and flortaucipir PET studies were conducted on sub‐samples of the cohort along with appropriate control participants.ResultPeak flortaucipir standard uptake value ratio (SUVR) among A431E mutation carriers was predominantly in the lateral parietal cortices relative to the medial temporal lobes with disproportionate signal in motor and sensory cortex relative to persons with late onset AD. Flortaucipir SUVR in 6 brain regions (i.e., medial orbitofrontal, caudal and rostral anterior cingulate, parahippocampal, precuneus, and lateral occipital) were associated with neuropsychiatric symptoms in persons with or at risk for the A431E PSEN1 mutation. Among 21 A431E PSEN1 mutation carriers with available diffusion MRI images, the Ashworth score of spastic paraparesis correlated with mean diffusivity in several brain regions, particularly left inferior parietal, superior parietal, and paracentral lobules (r’s&gt;0.8, p’s&lt; 0.001). In a subset of 10 clinically impaired A431E PSEN1 mutation carriers, mean diffusivity in white matter tracts underlying multiple cortical areas was higher relative to 8 impaired persons with late onset AD or ADAD mutations that do not cause spastic paraparesis.ConclusionThe pattern of flortaucipir distribution was atypical with disproportionate involvement of sensorimotor areas and parietal cortex. Higher flortaucipir signal was associated with more neuropsychiatric symptoms. Microstructural changes in white matter were more pronounced in persons with the A431E PSEN1 mutation and likely underlie the associated spastic paraparesis. The distinct neuroimaging features and associated neuropsychiatric manifestations observed in this cohort highlight the importance of comprehensively characterizing heterogeneous AD subtypes.

TMS and imaging correlates of spasticity in persons at‐risk for the A431E PSEN1 mutation

AbstractBackgroundSpastic paraparesis (SP) occurs in approximately 45% of carriers of the A431E PSEN1 mutation (MCs), sometimes preceding cognitive decline. SP is typically caused by reduced cortical excitatory output to spinal motor neurons resulting from delayed cortical conduction time or increased inhibitory output from cortex. Previous studies have observed that people with spasticity have increased corticospinal inhibition at rest and altered interhemispheric inhibitory control (amount of inhibition and conduction time) during isometric contraction. Hence, in this study, we sought to identify transcranial magnetic stimulation (TMS) and diffusion MRI and flortaucipir PET imaging predictors of SP using these inhibitory measures captured using TMS.MethodWe included 19 persons known to be at‐risk for the A431E PSEN1 mutation (15 MCs, 3 NCs) and one person affected by the F388S PSEN1 mutation who participated in a comprehensive study of autosomal dominant AD including TMS, diffusion MRI, and flortaucipir PET. We measured cosrticospinal inhibition for lower limbs at rest by targeting tibialis anterior muscle representation at primary motor cortex. For inter‐hemispheric inhbition (extent of inhibition and transcallosal conduction time), we stimulated the hemisphere ipsilateral to the limb performing isometric contraction. We ran a non‐parametric regression model for prediction using the gsm function from the npreg package in R© because several variables were not normally distributed (Shapiro‐Wilk test, p&lt;0.05).ResultSpasticity score (Ashworth scale) was positively associated with interhemispheric inhibition, transcallosal conduction time, and DTI measures of the corticospinal tract and pre‐post‐para central lobes of both hemispheres (Spearman rank correlation, p&lt; 0.05). Among all inhibitory TMS measures and DTI variables, the transcallosal conduction time for the lower limbs (β = 2.87) and suvr_rh_paracentral (β = ‐25.92) independently predicted increased spasticity scores. The interaction effect between these measures was insignificant. The prediction model had an adjusted R2 value of 0.89.ConclusionWe show increased transcallosal conduction time and decreased white matter integrity around the right‐hemisphere paracentral lobule is associated with increased mean spasticity scores in people with A431E PSEN1 mutations. This is consistent with other studies showing altered interhemispheric control in SP. Delay in transcallosal conduction time in A431E PSEN1 MCs may compromise inter‐hemispheric control limiting smooth movement control.

Elevated cerebrospinal fluid chitinase‐3 protein like‐1 (YKL‐40) is associated with decreased glucose metabolism in amyloid‐positive participants.

AbstractBackgroundThe diverse role played by astrocytes in neurodegeneration remains elusive. Astrocytes elicit a substantial impact on the fluorodeoxyglucose (FDG)‐positron emission tomography (PET) signal, an imaging modality that is used as a surrogate marker for neuronal loss. The association between astrocyte activation and FDG‐PET uptake has been evaluated with astrocyte‐targeting PET. Measuring reactive astrocytosis with fluid biomarkers may be a simpler and affordable way of studying astrocytes and their association with FDG‐PET. The cerebrospinal fluid (CSF) biomarker chitinase‐3 protein like‐1 (YKL‐40), a marker of reactive astrocytosis is elevated in the CSF of AD patients, although its role is unclear. Here, we examined the relationship between CSF YKL‐40 and PET imaging markers across the AD continuum.Method421 participants, including 89 patients with AD, 234 patients with mild cognitive impairment (MCI), and 98 cognitively normal control (CN) participants were selected from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database based on the availability of coinciding amyloid (Aβ)‐PET, FDG‐PET and structural magnetic resonance imaging (MRI), and CSF YKL‐40. The relationships between CSF YKL‐40 and PET imaging markers were explored using both a region of interest (ROI) and a voxel‐wise approach.ResultAD patients demonstrated elevated CSF YKL‐40 compared to CN (p&lt;0.001) and MCI (p&lt;0.001) participants. CSF YKL‐40 was also significantly elevated in Aβ positive participants (p&lt;0.001). ROI analysis revealed negative associations between CSF YKL‐40 and FDG‐PET uptake throughout the cortex in Aβ positive participants but limited to the cingulate cortex in Aβ negative participants. At a voxel‐level, Aβ‐PET uptake was positively associated with CSF YKL‐40 in Aβ positive participants. Meanwhile, a negative association was observed between CSF YKL‐40 and FDG‐PET across the brain in Aβ positive participants, a relationship lost in Aβ negative participants.ConclusionCSF YKL‐40 levels likely become elevated as AD progresses due to gradual amyloid deposition. Contrary to previous findings, reactive astrocytosis, as measured here with CSF YKL‐40, was associated with a reduction in glucose metabolism in amyloid positive participants, possibly due to the damaged caused to neurons by the AD pathology.

P143: New therapies for Alzheimer’s dementia and its implications on healthcare system: are we ready?

Objective:The amyloid hypothesis suggests that errors in production, accumulation, or disposal of beta-amyloid are the primary causes of Alzheimer's disease (AD). Since this was hypothesized, there has been significant effort in developing treatments that prevent the build-up of amyloid beta (Aβ) plaques in the brain. A disease modifying therapy (DMT) changes the clinical progression of AD by interfering in its pathophysiological mechanisms.The aim of this article is to review the current literature regarding the role of new DMTs for Alzheimer’s dementia and assess the preparedness of health care systems to implement these treatment options.Methods:Review of the most recent literature regarding the role of new DMTs for Alzheimer’s dementia and the challenges faced by the health care system to implement these treatment options. The research was carried out through the PubMed and UptoDate databases, using the terms “amyloid hypothesis”, “Alzheimer”, “disease modifying treatments” and “dementia”.Results:Research has been focusing on developing monoclonal antibodies as potential DMTs that target Aβ. Aducanumab, a human antibody, or immunotherapy, is the only disease-modifying medication currently approved to treat AD. It targets the Aβ protein and helps to reduce amyloid plaques and is currently the only FDA approved medication to slow the progression of AD. Lecanemab, a humanized IgG1 monoclonal antibody, binds to Aβ soluble protofibrils with high affinity. Even though there is considerable optimism about its potential, lecanemab will probably be more useful to patients on early stages of the disease.Conclusion:DMTs administration obeys to certain needs such as a vacancy in Day Hospital for infusion and regular monitorization and for lumbar punction. It demands a complex network involving general practitioner, neurologist, psychiatrist, psychologist, and social services. It also involves a genetic study and complementary diagnosis exams such as PET (Positron emission tomography) scans and MRIs (Magnetic resonance imaging), which are expensive. There is an emerging need to develop enhanced and safer treatments.