Positron Emission Tomography Results Research Articles

Research Participants' Perspectives on Precision Diagnostics for Alzheimer's Disease.

Understanding research participants' responses to learning Alzheimer's disease (AD) risk information is important to inform clinical implementation of precision diagnostics given rapid advances in disease modifying therapies. We assessed participants' perspectives on the meaning of their amyloid positron emission tomography (PET) imaging results for their health, self-efficacy to understand their results, psychological impact of learning their results, experience receiving their results from the clinical team, and interest in genetic testing for AD risk. We surveyed individuals who were being clinically evaluated for AD and received PET imaging six weeks after the return of results. We analyzed responses to close-ended survey items by PET result using Fisher's exact test and qualitatively coded open-ended responses. A total of 88 participants completed surveys, most of whom had mild cognitive impairment due to AD (38.6%), AD (28.4%), or were cognitively unimpaired (21.6%). Participants subjectively understood their results (25.3% strongly agreed, 41.8% agreed), which could help them plan (16.5% strongly agreed, 49.4% agreed). Participants with a negative PET result (n = 25) reported feelings of relief (Fisher's exact p < 0.001) and happiness (p < 0.001) more frequently than those with a positive result. Most participants felt that they were treated respectfully and were comfortable voicing concerns during the disclosure process. Genetic testing was anticipated to be useful for medical care decisions (48.2%) and to inform family members about AD risk (42.9%). Participants had high subjective understanding and self-efficacy around their PET results and did not experience negative psychological effects. Interest in genetic testing was high.

Exploring the mechanism of 18F-fluorodopa uptake in recurrent high-grade gliomas: A comprehensive histomolecular-positron emission tomography analysis.

Dihydroxy-6-[18F]fluoro-L-phenylalanine (18F-FDOPA) positron emission tomography (PET) is a valuable tool for managing high-grade gliomas (HGGs), but there is a lack of literature on its relationship with glioma subtypes since the 2021 reclassification of brain tumors. There is also debate surrounding the mechanism of 18F-FDOPA uptake, particularly after chemoradiation therapy. This study aimed to investigate the correlation between 18F-FDOPA uptake and histomolecular characteristics, particularly L-amino acid transporter 1 (LAT1) expression, in recurrent gliomas, and examine their impact on survival in HGGs. Thirty-nine patients with recurrent HGGs (14 isocitrate dehydrogenase [IDH]-mutant, 25 IDH-wildtype) who underwent a brain 18F-FDOPA PET/computed tomography (CT) or PET/magnetic resonance imaging (MRI) followed by surgical resection of the 18F-FDOPA-avid lesion within 6 months, were retrospectively reviewed. PET results were compared with histological examination and for SCL7A5/LAT1 immunostaining. The study also examined the relationship between PET parameters, LAT1 expression, and survival outcomes. Astrocytoma IDH-mutant G4 had higher 18F-FDOPA uptake than glioblastoma IDH-wildtype G4 (maximum tumor-to-normal brain ratio [TBRmax] 5 [3.4-9] vs. 3.8 [2.8-5.9], p = 0.02). IDH-mutant gliomas had higher LAT1 expression than IDH-wildtype gliomas (100 [14-273] vs. 15.5 [0-137], p < 0.05) as well as higher TBRmax (5 [2.4-9] vs. 3.8 [2.8-6], p < 0.05). In survival analysis, LAT1 score >100 was a predictor for longer progression-free survival in IDH-mutant HGGs. To our knowledge, our study is the first to suggest a link between LAT1 expression and IDH mutation status. We showed that higher TBRmax was associated with higher LAT1 expression and IDH mutation status. Further studies are needed to better understand the mechanisms underlying amino acid PET tracers uptake, especially in the post-radiation and chemotherapy settings.

Amyloid Positron Emission Tomography and Subsequent Health Care Use Among Medicare Beneficiaries With Mild Cognitive Impairment or Dementia

Results of amyloid positron emission tomography (PET) have been shown to change the management of patients with mild cognitive impairment (MCI) or dementia who meet Appropriate Use Criteria (AUC). To determine if amyloid PET is associated with reduced hospitalizations and emergency department (ED) visits over 12 months in patients with MCI or dementia. This nonrandomized controlled trial analyzed participants in the Imaging Dementia-Evidence for Amyloid Scanning (IDEAS) study, an open-label, multisite, longitudinal study that enrolled participants between February 2016 and December 2017 and followed up through December 2018. These participants were recruited at 595 clinical sites that provide specialty memory care across the US. Eligible participants were Medicare beneficiaries 65 years or older with a diagnosis of MCI or dementia within the past 24 months who met published AUC for amyloid PET. Each IDEAS study participant was matched to a control Medicare beneficiary who had not undergone amyloid PET. Data analysis was conducted on December 13, 2022. Participants underwent amyloid PET at imaging centers. The primary end points were the proportions of patients with 12-month inpatient hospital admissions and ED visits. One of 4 secondary end points was the rate of hospitalizations and rate of ED visits in participants with positive vs negative amyloid PET results. Health care use was ascertained from Medicare claims data. The 2 cohorts (IDEAS study participants and controls) each comprised 12 684 adults, including 6467 females (51.0%) with a median (IQR) age of 77 (73-81) years. Over 12 months, 24.0% of the IDEAS study participants were hospitalized, compared with 25.1% of the matched control cohort, for a relative reduction of -4.49% (97.5% CI, -9.09% to 0.34%). The 12-month ED visit rates were nearly identical between the 2 cohorts (44.8% in both IDEAS study and control cohorts) for a relative reduction of -0.12% (97.5% CI, -3.19% to 3.05%). Both outcomes fell short of the prespecified effect size of 10% or greater relative reduction. Overall, 1467 of 6848 participants (21.4%) with positive amyloid PET scans were hospitalized within 12 months compared with 1081 of 4209 participants (25.7%) with negative amyloid PET scans (adjusted odds ratio, 0.83; 95% CI, 0.78-0.89). Results of this nonrandomized controlled trial showed that use of amyloid PET was not associated with a significant reduction in 12-month hospitalizations or ED visits. Rates of hospitalization were lower in patients with positive vs negative amyloid PET results.

In Situ Measurements of Dynamic Bacteria Transport and Attachment in Heterogeneous Sand-Packed Columns.

Prevention, mitigation, and regulation of bacterial contaminants in groundwater require a fundamental understanding of the mechanisms of transport and attachment in complex geological materials. Discrepancies in bacterial transport behaviors observed between field studies and laboratory experiments indicate an incomplete understanding of dynamic bacterial transport and immobilization processes in realistic heterogeneous geologic systems. Here, we develop a new experimental approach for in situ quantification of dynamic bacterial transport and attachment distribution in geologic media that relies on radiolabelingEscherichia coliwith positron-emitting radioisotopes and quantifying transport with three-dimensional (3D) positron emission tomography (PET) imaging. Our results indicate that the highest bacterial attachment occurred at the interfaces between sand layers oriented orthogonal to the direction of flow. The predicted bacterial attachment from a 3D numerical model matched the experimental PET results, highlighting that the experimentally observed bacterial transport behavior can be accurately captured with a distribution of a first-order irreversible attachment model. This is the first demonstration of the direct measurement of attachment coefficient distributions from bacterial transport experiments in geologic media and provides a transformational approach to better understand bacterial transport mechanisms, improve model parametrization, and accurately predict how local geologic conditions can influence bacterial fate and transport in groundwater.

Perspectives From Black and White Participants and Care Partners on Return of Amyloid and Tau PET Imaging and Other Research Results.

Alzheimer disease (AD) biomarker testing is now common in research and approaching clinical translation. Disclosure protocols must be informed by diverse participants' perspectives on if/how the information would be useful. This study utilized semistructured interviews assessing interest in receiving positron emission tomography (PET) amyloid and tau results, as well as perceived risks and benefits of hypothetical PET disclosure as a function of race and participant diagnosis. Participants [39% Black; 61% White; Mage =74.28 (5.98)] included 57 adults diagnosed as either cognitively healthy (58%) or with mild cognitive impairment (42%) and their respective care partners [33% Black; 67% White; Mage =66.93 (10.92)]. Most dyads endorsed strong interest in PET results (82.5% of both participants and partners) regardless of race or diagnosis. Black care partners were less interested in receiving the participant's results than White care partners ( χ2(4) =8.31, P =0.047). Reasons for disclosure were diverse and highly personalized, including access to treatments or clinical trials (23.2% participants; 29.8% partners), advance planning (14.3% participants; 17.5% partners), and improved health knowledge (12.5% participants; 15.8% partners). In contrast, over 80% of respondents denied any risks of disclosure. Results suggest that predisclosure education, decisional capacity assessment, and a flexible disclosure approach are needed.

Diagnostic value of 18F-fluoro-2-deoxyglucose positron emission tomography/computed tomography imaging in acral melanoma-predominant Asian patients.

Tumor staging is crucial for melanoma, of which acral melanoma is the predominant subtype in Asians. 18F-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) and 18F-FDG-PET/computed tomography (18F-FDG-PET/CT) serve as non-invasive imaging tools for tumor staging. However, the literature is scarce on the diagnostic value of PET for acral melanoma. From January 1, 2006, to November 30, 2022, a total of 352 patients were diagnosed with melanoma at our hospital. Of them, 90 were diagnosed with cutaneous melanoma and underwent preoperative PET/CT for staging and sentinel lymph node biopsy or complete lymph node dissection. Staging of PET/CT was confirmed by histopathology or following imaging. The lymph node biopsy, distant metastasis status, and PET/CT imaging results were analyzed. Of all the 90 patients with cutaneous melanoma, 72 of them were diagnosed as acral melanoma(80.0%). Compared with the histopathologic results, the lymph nodes were true-positive, true-negative, false-positive, and false-negative in 12, 54, seven, and 17 cases, respectively. The sensitivity of PET/CT for local lymph nodes was 41.4% (95% confidence interval [CI], 23.5-61.1%), while its specificity was 88.5% (95% CI, 77.8-95.3%). As for the detection of distal metastasis, the PET results were true-positive, true-negative, false-positive, and false-negative in six, 65, 15, and four cases, respectively. The sensitivity of PET for distal metastasis detection was 60.0% (95% CI, 26.2-87.8%), while its specificity was 81.3% (95% CI, 71.0-89.1%). Although non-invasive, PET/CT has relatively low sensitivity in regional lymph node evaluations and fair sensitivity in distal metastasis detection in Asian patients with acral melanoma. Thus, PET/CT may be more useful in patients with clinically palpable nodes or more advanced disease stage.

Outcome prediction by interim positron emission tomography and IgM monoclonal gammopathy in diffuse large B-cell lymphoma.

In diffuse large B-cell lymphoma (DLBCL), a positive interim positron emission tomography (PET) scan predicts treatment failure, but the proportion of high-risk patients thus identified is small. To improve prediction, we combined the interim PET result with the presence or absence of an associated IgM gammopathy. Of 108 DLBCL patients participating in a prospective trial, nine (8%) were interim PET positive and 19 (18%) had an IgM gammopathy. The monoclonal protein was not associated with distinguishing genetic features, and its light chain restriction was not always concordant with the light chain restriction of the lymphoma. The information provided by interim PET and IgM gammopathy was combined to dichotomize the population into sizeable high-risk (1-2 adverse factors) and low-risk groups (no adverse factor) with widely different outcomes (population size, 25% vs. 75%; 3-year risk of progression, 51% vs. 10%; 3-year overall survival, 64% vs. 95%). Multivariable analyses including established risk factors revealed the interim PET result and the IgM gammopathy status to be the only factors significantly associated with outcome. Information about interim PET response and IgM gammopathy may be useful in studies testing risk-adapted treatment strategies.

Analysis of Positive Results of 18F-FDG PET/CT Imaging after Hematopoietic Stem Cell Transplantation in Lymphoma.

The purpose of this study was to differentiate between false-positive and true-positive positron emission tomography (PET) results after hematopoietic stem cell transplantation (SCT) for lymphoma involvement by analyzing several clinical variables and specific imaging features. Patients with lymphoma who received SCT and underwent post-transplantation 18F-FDG PET/CT scans between January 2013 and April 2021 at our institution were included. Associations between PET positivity and related clinical information were assessed using t-tests and χ2 tests. The significance of variables differentiating benign lesions from malignant FDG-avid lesions was evaluated by logistic regression analysis. Survival probabilities were derived from Kaplan-Meier curves and compared using the log-rank test. A total of 185 patients (235 post-transplantation PET/CT scans) were enrolled in our present study. Compared with those with true-positive PET results, patients with false-positive PET results exhibited a better prognosis. For the autologous SCT group, false-positive cases were more commonly seen when FDG-avid foci appeared outside the sites of the original disease (p = 0.004), and the integrated CT imaging showed negative results (p = 0.000). In multivariate logistic regression analysis, integrated CT results were the only significant factor. For the allogeneic SCT group, false-positive cases were significantly more commonly seen when DS = 4 (p = 0.046), FDG-avid foci appeared outside the sites of the original disease (p = 0.022), and the integrated CT imaging showed negative results (p = 0.001). In a multivariate logistic regression analysis, whether FDG-avid foci were in the sites of the original disease and integrated CT results were both significant factors. False-positive FDG uptake in post-transplantation PET was not uncommon. Several variables could provide an important reference to differentiate false-positive from true-positive post-SCT PET results for lymphoma involvement. ChiCTR2300067355.

Comparative pathological study of Carbon‐11 labeled Pittsburgh compound‐B PET Centiloid Scale and amyloid beta deposition in postmortem brains

AbstractBackgroundCentiloid Scale (CL) was developed to standardize the quantitative results of amyloid beta (Aβ) positron emission tomography (PET). CL can allow not only categorization of the binary results of amyloid PET as positive or negative, but also parametric weighting within each category. To date, several neuropathological studies evaluated the performance of CL, but further validation studies of the Asian population, elderly cohorts, and relatively short intervals between PET scanning and autopsy may be required.MethodTwenty‐two consecutive autopsy cases registered to the Brain Bank for Aging Research, who received Carbon‐11 labeled Pittsburgh compound‐B PET were included. Amyloid PET results of CL were compared with the final neuropathological diagnosis and the grading of Aβ deposition.ResultThe mean age of the 22 patients at death was 81.0 (SD: 8.4) years, seven of whom fulfilled pathological diagnosis of Alzheimer’s disease (AD). The mean interval from PET to autopsy was 17.5 (SD: 15.3) months. The mean CL was higher in the AD group (88.5 [SD: 30.9]) than in the non‐AD group (9.7 [SD: 25.6], p &lt;0.001). Cutoff value of 50 could segregated seven AD and two non‐AD patients above and 13 non‐AD patients below. CL correlated with CERAD plaque score, Thal phase, and Braak amyloid stage with polyserial correlation coefficient of 0.93, 0.87, and 0.87, respectively. The lower limit of the CL value corresponding to moderate to frequent CERAD plaque score or equal to or more than Thal phase 4 was 17.31.ConclusionThe CL value is in good agreement with the extent of Aβ accumulation. The cutoff value for predicting moderate or greater accumulation of Aβ was 15‐20, and the cutoff value for predicting AD pathology was 50‐60. Further accumulation and integration of data will allow us to establish more appropriate cutoff value.

Evaluation of Plasma Phosphorylated Tau217 for Differentiation Between Alzheimer Disease and Frontotemporal Lobar Degeneration Subtypes Among Patients With Corticobasal Syndrome

Plasma phosphorylated tau217 (p-tau217), a biomarker of Alzheimer disease (AD), is of special interest in corticobasal syndrome (CBS) because autopsy studies have revealed AD is the driving neuropathology in up to 40% of cases. This differentiates CBS from other 4-repeat tauopathy (4RT)-associated syndromes, such as progressive supranuclear palsy Richardson syndrome (PSP-RS) and nonfluent primary progressive aphasia (nfvPPA), where underlying frontotemporal lobar degeneration (FTLD) is typically the primary neuropathology. To validate plasma p-tau217 against positron emission tomography (PET) in 4RT-associated syndromes, especially CBS. This multicohort study with 6, 12, and 24-month follow-up recruited adult participants between January 2011 and September 2020 from 8 tertiary care centers in the 4RT Neuroimaging Initiative (4RTNI). All participants with CBS (n = 113), PSP-RS (n = 121), and nfvPPA (n = 39) were included; other diagnoses were excluded due to rarity (n = 29). Individuals with PET-confirmed AD (n = 54) and PET-negative cognitively normal control individuals (n = 59) were evaluated at University of California San Francisco. Operators were blinded to the cohort. Plasma p-tau217, measured by Meso Scale Discovery electrochemiluminescence, was validated against amyloid-β (Aβ) and flortaucipir (FTP) PET. Imaging analyses used voxel-based morphometry and bayesian linear mixed-effects modeling. Clinical biomarker associations were evaluated using longitudinal mixed-effect modeling. Of 386 participants, 199 (52%) were female, and the mean (SD) age was 68 (8) years. Plasma p-tau217 was elevated in patients with CBS with positive Aβ PET results (mean [SD], 0.57 [0.43] pg/mL) or FTP PET (mean [SD], 0.75 [0.30] pg/mL) to concentrations comparable to control individuals with AD (mean [SD], 0.72 [0.37]), whereas PSP-RS and nfvPPA showed no increase relative to control. Within CBS, p-tau217 had excellent diagnostic performance with area under the receiver operating characteristic curve (AUC) for Aβ PET of 0.87 (95% CI, 0.76-0.98; P < .001) and FTP PET of 0.93 (95% CI, 0.83-1.00; P < .001). At baseline, individuals with CBS-AD (n = 12), defined by a PET-validated plasma p-tau217 cutoff 0.25 pg/mL or greater, had increased temporoparietal atrophy at baseline compared to individuals with CBS-FTLD (n = 39), whereas longitudinally, individuals with CBS-FTLD had faster brainstem atrophy rates. Individuals with CBS-FTLD also progressed more rapidly on a modified version of the PSP Rating Scale than those with CBS-AD (mean [SD], 3.5 [0.5] vs 0.8 [0.8] points/year; P = .005). In this cohort study, plasma p-tau217 had excellent diagnostic performance for identifying Aβ or FTP PET positivity within CBS with likely underlying AD pathology. Plasma P-tau217 may be a useful and inexpensive biomarker to select patients for CBS clinical trials.

Modern approaches to the diagnosis and treatment of cardiac sarcoidosis: results of a cohort study

Aim. To analyze clinical and paraclinical data in patients with documented cardiac sarcoidosis, outlining the key points of diagnosis and selection of the optimal treatment.Material and methods. For the period from 2016 to 2021, 63 patients (50,4±14,1 years) were included in the cohort study on negotiability. Based on a standard examination, 15 patients (41±13 years old) were selected, who continued the examination to confirm the diagnosis of cardiac sarcoidosis. Contrast-enhanced cardiac magnetic resonance imaging (MRI) was performed in 10 patients, while endomyocardial biopsy in 7 patients. All patients underwent 18F-fluorodeoxyglucose positron emission tomography (PET).Results. The most common (53%) electrocardiographic abnormality was right bundle branch block. Ventricular arrhythmias and high-grade atrioventricular block were recorded mainly in patients with documented activity. Regional contractility disorders were predominantly detected in patients with cardiac fibrosis. Delayed contrast enhancement according to cardiac MRI was recorded mainly intramurally in the interventricular septum and subepicardial area of left ventricular (LV) lateral wall. When analyzing the PET results, we found the predominant radiopharmaceutical accumulation in the interventricular septum (56%), lateral (44%) and anterior (33%) LV walls. There was no significant improvement in global LV contractility against the background of immunosuppressive therapy, especially in patients with reduced ejection fraction: initially 49,2±10,1% vs 46,9±14,9% during therapy (p=0,658).Conclusion. A certain apprehensive attitude of the doctor and adherence to the algorithm for early diagnosis of cardiac sarcoidosis allows minimizing the risks of fatal cardiovascular events. On the contrary, in the case of late diagnosis, even the use of aggressive immunosuppressive therapy does not lead to an improvement in global myocardial contractility, and fibrosis zones can cause life-threatening bradyarrhythmias and ventricular arrhythmias.

Extension of microglial activation is associated with epilepsy and cognitive dysfunction in Tuberous sclerosis complex: A TSPO-PET study

Background and objectivesNeuroinflammation contributes to the severity of various neurological disorders, including epilepsy. Tuberous sclerosis complex (TSC) is a condition that results in the overactivation of the mammalian target of rapamycin (mTOR) pathway, which has been linked to the activation of microglia responsible for neuroinflammation. To clarify the involvement of neuroinflammation in the neuropathophysiology of TSC, we performed a positron emission tomography (PET) study using the translocator protein (TSPO) radioligand, [11C] DPA713, and investigated microglial activation in relation to neurological manifestations, especially epilepsy and cognitive function. MethodsThis cross-sectional study included 18 patients with TSC (6 in the no-seizure group, 6 in the refractory seizure group, and 6 in the mTOR-inhibitor [mTOR-i] group). All participants underwent [11C] DPA713-PET. PET results were superimposed with a 3D T2-weighted fluid-attenuated inversion-recovery (FLAIR) and T1-weighted image (T1WI) to evaluate the location of cortical tubers. Microglial activation was assessed using the standardized uptake value ratio (SUVr) of DPA713 binding. The volume ratio of the DPA713-positive area to the intracranial volume (volume ratio of DPA713/ICV) was calculated to evaluate the extent of microglial activation. A correlation analysis was performed to examine the relationship between volume ratio of DPA713/ICV and severity of epilepsy and cognitive function. ResultsMost cortical tubers with hyperintensity on FLAIR and hypo- or isointensity on T1WI showed microglial activation. The extent of microglial activation was significantly greater in the refractory seizure group than in the no-seizure or mTOR-i groups (p < 0.001). The extent of microglial activation in subjects without mTOR-i treatment correlated positively with epilepsy severity (r = 0.822, P = 0.001) and negatively with cognitive function (r = -0.846, p = 0.001), but these correlations were not present in the mTOR-i group (r = 0.232, P = 0.658, r = 0.371, P = 0.469, respectively). ConclusionNeuroinflammation is associated with the severity of epilepsy and cognitive dysfunction in brains with TSC. mTOR-i may suppress the extent of neuroinflammation in TSC. Investigating the spread of microglial activation using TSPO-PET in these patients may help to predict the progression of neuropathy by assessing the degree of neuroinflammation and therefore be useful for determining how aggressive the treatment should be and in assessing the effectiveness of such treatment in patients with TSC.

Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography–based Lymph Node Atlas for Salvage Radiotherapy in Patients with Recurrent Prostate Cancer: A Validation of the New NRG Oncology 2020 guideline

BackgroundApproximately 20–40% of patients with prostate cancer (PC) who undergo radical prostatectomy (RP) experience relapse, with the majority of these cases developing pelvic lymph node (LN) metastases. Taking new data from the prostate-specific membrane antigen (PSMA) positron emission tomography (PET) era into account, the Radiation Therapy Oncology Group (RTOG) 2009 contouring guideline for the pelvic LNs from 2009 was updated by the NRG Oncology group in 2020 (NRG 2020). ObjectiveTo evaluate and validate the updated NRG 2020 guideline with our established LN atlas. Design, setting, and participantsWe screened 1653 PSMA PET/computed tomography (CT) data sets for patients with biochemical relapse who underwent a PET scan between November 2012 and November 2017. After screening, we developed an LN atlas using data from 233 patients. Outcome measurements and statistical analysisWe evaluated LN overlap (OL) with the RTOG 2009 and NRG 2020 contouring guidelines. OL was defined as within (>90%), partly within (10–90%), or outside (<10%). Results and limitationsIn comparison to the RTOG 2009 guideline, 403 (52%), 134 (17%), and 241 (31%) of the LNs were not, were partly, or were fully covered within the overall group, respectively. By contrast, using the NRG 2020 guideline, 302 (39%), 190 (24%), and 286 (37%) of the LNs were not, were partly, or were fully covered, respectively (p < 0.001). Limitations include the retrospective design with missing data and no histopathological confirmation of the PET results. ConclusionsThe updated NRG 2020 contouring guideline improves coverage of the pelvic LNs in patients undergoing salvage radiation therapy. However, PET/CT should be considered whenever possible to ensure coverage of untypical LN spread. Patient summaryWe compared the 2009 and 2020 guidelines on the radiation area for the pelvis for patients with recurrent prostate cancer that has spread to lymph nodes. The newer guideline provides better coverage of pelvic lymph nodes than the older one and is useful in planning radiation therapy. However, a scan of the pelvis using the newest technique should be considered for individual patients to ensure coverage of untypical lymph nodes.

Warranty period of normal CCTA and [15O]H2O PET in chest pain patients

Abstract Background Normal coronary computed tomography angiography (CTA) and positron emission tomography (PET) are associated with an excellent prognosis. Hitherto, data on the warranty period of normal coronary CTA and normal myocardial blood flow (MBF) by PET are scarce. Purpose To determine the event-free period after normal coronary CTA and PET results. In addition, to determine whether PET MBF imaging confers additional prognostic value beyond coronary anatomy in symptomatic patients. Methods Patients with suspected but not previously diagnosed coronary artery disease (CAD) who underwent coronary CTA or [15O]H2O PET were categorized based upon coronary CTA as no CAD, non-obstructive CAD or obstructive CAD. A hyperemic MBF &amp;lt;2.3 ml/min/g was considered abnormal and indicative for ischemia. A cumulative risk below 5% against death and myocardial infarction (MI) was used to define the warranty period. Results Of 2575 included patients (mean age 61.4±9.9 years, 41% male) 1319 (51.2%) underwent coronary CTA only, 1237 (48.0%) underwent both coronary CTA and PET and 19 (0.74%) patients underwent PET imaging only. During a median follow-up of 7.0 years 163 deaths and 68 MIs occurred. The warranty period for patients without any CAD was &amp;gt;10 years. Patients with non-obstructive CAD had a 5 year warranty period. In patients with no, non-obstructive or obstructive CAD on CTA, normal PET extended the warranty period with ≥2 years. The warranty period of patients with non-obstructive CAD or normal perfusion varied between 2.5 and &amp;gt;10 years for patients with or without clinical risk factors. Conclusions As standalone imaging, the warranty period for a normal coronary CTA is &amp;gt;10 years, whereas patients with non-obstructive CAD have a warranty period of 5 years. Independent of coronary anatomy normal perfusion imaging has additional prognostic value and extends the warranty period by ≥2 years. Funding Acknowledgement Type of funding sources: None.

Comparison of second-line on-site computed quantitative flow ratio from coronary computed tomography angiography to PET perfusion imaging for detecting obstructive coronary artery disease

Abstract Introduction In patients with suspected obstructive coronary artery disease (CAD) on coronary computed tomography (CTA), guidelines endorse second-line selective testing for hemodynamic evaluation of suspected CAD. A variety of non-invasive modalities are available, and myocardial perfusion imaging with Rubidium-82 positron emission tomography (PET) is an established method with high diagnostic performance. Recently, an on-site method estimating computed tomography-derived quantitative flow ratio (CT-QFR) showed promising results for discriminating obstructive CAD. However, no study has compared the diagnostic performances of PET and CT-QFR. Purpose To assess a possible non-inferiority of CT-QFR compared to PET in patients with suspected obstructive CAD at CTA using invasive coronary angiography (ICA) with fractional flow reserve (FFR) as reference. Methods Patients (n=1732, 57% males, age 59±9.5) referred on a clinical indication with symptoms suggestive of obstructive CAD underwent routine CTA. Patients with ≥50% diameter stenosis (DS) on CTA were referred for PET and subsequent ICA with FFR. CT-QFR was analyzed post-hoc blinded to PET and ICA results. Abnormal CT-QFR was defined as CT-QFR ≤0.80 in any vessel with a diameter ≥1.5mm. An independent core-lab evaluated PET scans as abnormal/normal with optional analyst-dependent application of pre-specified criteria; summed stress score of ≥4 in ≥2 contiguous segments, vessel-specific myocardial blood flow (MBF) &amp;lt;2.00 ml/g/min, global myocardial blood flow reserve ≤1.8, and/or transient ischemic dilatation ratio &amp;gt;1.13. Obstructive CAD was defined as ICA with FFR ≤0.80 or high-grade stenosis (≥90% DS). Results In total, 445/1732 patients (25%) had suspected obstructive CAD on CTA of whom 400/445 patients (90%) underwent subsequent PET and ICA. CT-QFR was successfully analysed in 383/400 (96%) patients classifying 174/383 (45%) patients as having disease. In comparison, PET classified 130/383 (34%) patients as having disease. In total, obstructive CAD by ICA with FFR was identified in 162 (42%) patients. There was no significant difference in area under the receiver-operating characteristic curves for CT-QFR compared to the best performing PET metric (lowest vessel-specific MBF); 0.84 (95% CI 0.80–0.89) vs. 0.81 (0.77–0.85), p=0.19)) (Fig. 1). Overall diagnostic accuracy of CT-QFR versus PET was similar (78% (95% CI 74–82) vs. 77% (72–81), p=0.70. Sensitivities for CT-QFR and PET were 78% (71–84) and 63% (55–70), p&amp;lt;0.01, respectively, and specificities 78% (72–84) and 87% (82–91), p=0.01, respectively (Fig. 2). Three-vessel or left main disease on ICA was correctly identified in 30/31 patients by both CT-QFR and PET. Conclusion In patients with suspected obstructive CAD by CTA, second-line CT-QFR was non-inferior to PET for discriminating obstructive CAD by invasive FFR; Although diagnostic accuracy was similar, CT-QFR demonstrated higher sensitivity while PET showed higher specificity Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Aarhus University PhD fellowshipRegion Mid Health Research Foundation

P008: Impact of bone marrow involvement on early PET response and progression-free survival in the HD18 trial for patients with advanced-stage Hodgkin lymphoma

Background: The prognostic role of bone marrow (BM) involvement in advanced-stage Hodgkin lymphoma is unclear, particularly for patients receiving intensive first-line treatment. We thus retrospectively examined its impact on early response and progression-free survival (PFS) among individuals receiving escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP) in the HD18 trial. Patients and Methods: A total of 424 individuals were suitable for analysis, of which 124 (29%) had BM involvement according to initial positron emission tomography (PET). Patient outcome was measured by PET response after 2×eBEACOPP and five-year PFS rate. Results: After 2×eBEACOPP, 79 of the BM PET-negative individuals (26%) and 26 of the BM PET-positive patients (21%) were found to be PET-positive (odds ratio [OR] 0.74, P=0.25). The five-year PFS rate was 90.7% in BM PET-negative individuals and 91.8% for BM PET-positive patients (hazard ratio 0.82, P=0.6). In our BM PET-positive subgroup, nine (16%) of the 56 subjects with one or two sites of skeletal uptake were PET-positive after 2×eBEACOPP as compared to 17 (25%) of the 68 individuals showing three or more BM lesions (OR 1.74, P=0.23). Conclusions: The present analysis demonstrates that BM involvement, irrespective of its extent, does not lead to increased risk for a positive interim PET result or inferior PFS in advanced-stage Hodgkin lymphoma patients undergoing eBEACOPP treatment. Skeletal lesions cannot therefore be considered as an additional prognostic marker of therapy failure or disease recurrence for individuals receiving intensive first-line treatment.

ABCL-007 Semiquantitative Measurements of Standard-Uptake-Value (ΔSUV) in Assessment of Patients Response and Outcomes in Aggressive Lymphomas

Positron emission tomography (PET) with 18-fluoro-2-deoxy-D-glucose ([18 F] FDG) is an essential tool for accurate staging, early, and late therapy response assessment in all FDG-avid lymphomas. To evaluate the accuracy of ΔSUV max in assessment of response to treatment in patients with lymphoma. This study was conducted between October 2019 and October 2021. Seventy-three patients diagnosed as high-grade lymphoma or Hodgkin disease (HD) were enrolled in the study. PET/CT examinations were performed at baseline (PET0), after the second, the fourth cycle of chemotherapy and at the end of treatment. PET-CT scans were analyzed according to the Deauville 5-point scale (5-PS). According to SUV-based assessment, PET/CT was considered negative when ΔSUV max at 2nd cycle (PET0-2) is more than 66% and ΔSUV max at 4th cycle (PET0-4) is more than 70%, respectively. The change in activity (ΔSUV) from initial (SUVmax1) to later scans (SUVmax2) was calculated as: SUV (%) = 100 x ([SUVmax2/SUVmax1] -1). Biopsy was taken if PET 2 or 4 is visually positive with negative delta SUV max, or in case of new lesions if other sites have improved. SUV uptake values at baseline were 16.30 ± 9.36 in NHL versus 12.55 ± 6.78 in HL. After 2 cycles of chemotherapy, (78.1%) had negative PET based on ΔSUV max raised to (86.3%) by the end of 4th cycle and this was different from 5PS where only (60.5%) raised to (74.4%) after the 4th cycle. In comparison with results of biopsy, ΔSUV0-2 has sensitivity 80%, specificity 94.1%, accuracy 90.91 % with P value (0.001) also, ΔSUV0-4 has sensitivity 80%, specificity 100%, accuracy 95.45 % with high agreement with P value (<0.001). On the contrary, the visual 5-PS analysis 0-2 specificity 17.65%, accuracy 36.36 with P value (<0.321). Also, the visual 5-PS analysis 0-4 specificity 41.18 %, accuracy 54.55% with P value (<0.082). After 4 cycles 22 patients needed to undergo biopsy because inconclusive results of PET. Comparison reveled that using ΔSUV max demonstrated higher specificity. ΔSUV max is comparable to biopsy and significantly more accurate than Deauville criteria in assessment of response to treatment.

Abstract 2479: Preclinical assessment of imaging agents for identification of fucosyl-GM1 expression in vivo

Abstract Background: Fucosyl-GM1 (FucGM1) is a monosialoganglioside highly expressed in 50%-70% of small cell lung cancer (SCLC) cells, supporting it as a potential biomarker. BMS-986012 is a nonfucosylated, first-in-class, fully human immunoglobulin G1 monoclonal antibody that binds to FucGM1 with high affinity and specificity. Understanding how FucGM1+ tumor expression correlates with response to BMS-986012 may improve patient selection and therapeutic efficacy. Objective: Evaluate ability of imaging agents built on BMS-986012 to detect tumor FucGM1 expression. Methods: BMS-986012 was labeled with a near-infrared fluorophore. Binding to human H520 (FucGM1−) and DMS79 (FucGM1+) xenografts was assessed in vivo via optical imaging. BMS-986012 was labeled with deferoxamine and radiolabeled to produce 89Zr-BMS-986279, which was evaluated in vitro with H520 and DMS79 cells. Tracer distribution and tumor accumulation was assessed by positron emission tomography (PET) imaging in mice bearing bilateral H520 and DMS79 xenografts and analyzed with ex vivo autoradiography (ARG). Results: Optical imaging with fluorescent BMS-986012 showed statistically significant accumulation in DMS79 vs H520 tumors at all time points (P&amp;lt;.05), beginning 6 hours post administration and reaching a 3:1 maximum uptake ratio. Maximum tumor to background signal was measured at 96 hours (final imaging time point). Total radiolabeled 89Zr-BMS-986279 binding to intact DMS79 cells was ≈15-fold higher than to H520 control cells in vitro and was almost completely blocked by coincubation with a 1000-fold excess of BMS-986012. In vivo, longitudinal PET imaging of 89Zr-BMS-986279 showed significantly higher tracer accumulation in FucGM1+ DMS79 xenografts vs H520 tumors (P&amp;lt;.001). The difference in tracer uptake between tumor models increased with time and was highest (≈2-fold) approximately 8 days post injection. PET signal decreased over time in both FucGM1− H520 xenografts and background muscle tissues, consistent with slow accumulation of specific binding and clearance from background common with antibody-based tracers. Ex vivo ARG studies confirmed in vivo PET results and indicated that 89Zr-BMS-986279 can be used to assess FucGM1 expression throughout the tumor volume, with signal found in the periphery and interior of tumor samples. Conclusions: In vitro cell binding, in vivo fluorescence and PET imaging, and ex vivo ARG studies demonstrated that 89Zr-BMS-986279 was sensitive and specific for detecting FucGM1 expression in tumor cells. Specificity to the intended target in animal disease models coupled with kinetics typical of antibody-based tracers further support the utility of 89Zr-BMS-986279 as a potential FucGM1 imaging agent. A phase 2 study is evaluating safety and efficacy of BMS-986012 combined with carboplatin, etoposide, or nivolumab in patients with newly diagnosed extensive-stage SCLC (NCT04702880). Citation Format: R. Adam Smith, Erin L. Cole, Andrea Olga Shorts, Thomas Petrone, Joonyoung Kim, Daniel Cohen, Paul Morin, Samuel J. Bonacorsi, Patrick L. Chow. Preclinical assessment of imaging agents for identification of fucosyl-GM1 expression in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2479.

Evaluation Algorithm for the Effectiveness of Stroke Rehabilitation Treatment Using Cross-Modal Deep Learning.

It is important to study the evaluation algorithm for the stroke rehabilitation treatment effect to make accurate evaluation and optimize the stroke disease treatment plan according to the evaluation results. To address the problems of poor restoration effect of positron emission tomography (PET) image and recognition restoration effect of evaluation data and so on. In the paper, we propose a stroke rehabilitation treatment effect evaluation algorithm based on cross-modal deep learning. Magnetic resonance images (MRI) and PET of stroke patients were collected as evaluation data to construct a multimodal evaluation dataset, and the data were divided into positive samples and negative samples. According to the mapping relationship between MRI and PET, three-dimensional cyclic adversarial is used to generate the neural network model to recover the missing PET data. Using the cross-modal depth learning network model, the RGB image, depth image, gray image, and normal images of MRI and PET are taken as the feature images and the multifeature fusion method is used to fuse the feature images, output the recognition results of MRI and PET, and evaluate the effect of stroke rehabilitation treatment according to the recognition results. The results show that the proposed algorithm can accurately restore PET images, the evaluation data recognition effect is good, and the evaluation data recognition accuracy is higher than 95%. The evaluation accuracy of stroke rehabilitation treatment effect is high, the evaluation time varies between 0.56 s and 0.91 s, and the practical application effect is good.

Multimodal neuroimaging of metabotropic glutamate 5 receptors and functional connectivity in alcohol use disorder.

People recovering from alcohol use disorder (AUD) show altered resting brain connectivity. The metabotropic glutamate 5 (mGlu5) receptor is an important regulator of synaptic plasticity potentially linked with synchronized brain activity and a target of interest in treating AUD. The goal of this work was to assess potential relationships of brain connectivity at rest with mGlu5 receptor availability in people with AUD at two time points early in abstinence. Forty-eight image data sets were acquired with a multimodal neuroimaging battery that included resting-state functional magnetic resonance imaging (fMRI) and mGlu5 receptor positron emission tomography (PET) with the radiotracer [18 F]FPEB. Participants with AUD (n=14) were scanned twice, at approximately 1 and 4weeks after beginning supervised abstinence. [18 F]FPEB PET results were published previously. Primary comparisons of fMRI outcomes were performed between the AUD group and healthy controls (HCs; n=23) and assessed changes over time within the AUD group. Relationships between resting-state connectivity measures and mGlu5 receptor availability were explored within groups. Compared to HCs, global functional connectivity of the orbitofrontal cortex was higher in the AUD group at 4weeks of abstinence (p=0.003), while network-level functional connectivity within the default mode network (DMN) was lower (p<0.04). Exploratory multimodal analyses showed that mGlu5 receptor availability was correlated with global connectivity across all brain regions (HCs, r=0.41; AUD group at 1week of abstinence, r=0.50 and at 4weeks, r=0.46; all p<0.0001). Furthermore, a component of cortical and striatal mGlu5 availability was correlated with connectivity between the DMN and salience networks in HCs (r=0.60, p=0.003) but not in the AUD group (p>0.3). These preliminary findings of altered global and network connectivity during the first month of abstinence from drinking may reflect the loss of efficient network function, while exploratory relationships with mGlu5 receptor availability suggest a potential glutamatergic relationship with network coherence.