18F-FDG PET Scans Research Articles

Advantages and limitations of 18-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography in the diagnosis of infective endocarditis

IntroductionThe early diagnosis of infective endocarditis (IE) is a medical challenge and a multidisciplinary approach is essential to improve its frequently fatal prognosis. Our goal was to evaluate the usefulness of [18F]2-fluoro-2-deoxy-d-glucose positron emission tomography (18F-FDG PET) in the diagnosis of this disease. Materials and MethodsWe prospectively assessed 43 patients (five female and 38 male) with clinical suspicion of IE between 2014 and 2017. All patients underwent transesophageal echocardiography (TEE) and an 18F-FDG PET scan, and the results were compared. A positive PET finding was defined as increased FDG uptake on cardiac valves or intracardiac devices. ResultsOut of 43 patients with suspected IE, the diagnosis was confirmed in 30 cases (79.7%). 18F-FDG PET was positive in 24 patients, with 19 showing FDG uptake on cardiac valves (two native and 17 prosthetic) and five on cardiac devices, being concordant with echocardiographic findings in 11 cases. 18F-FDG PET sensitivity was 80%, specificity 92%, positive predictive value (PPV) 96% and negative predictive value (NPV) 66%. Echocardiography presented sensitivity, specificity, PPV and NPV of 36%, 84%, 84% and 36%, respectively. Conclusions18F-FDG PET proved to be a sensitive technique with a high diagnostic value in patients with prosthetic valves and intracardiac devices and suspected IE. Its utility decreased dramatically in patients with suspected IE on native valves, in which TEE presented higher sensitivity and thus better diagnostic value.

A compressed sensing accelerated radial MS-CAIPIRINHA technique for extended anatomical coverage in myocardial perfusion studies on PET/MR systems

PurposeSimultaneous acquisition of myocardial first-pass perfusion MRI and 18F-FDG PET viability imaging on integrated whole-body PET/MR hybrid systems synergistically delivers both functional and metabolic information on the tissue state. While PET viability scans are inherently three-dimensional, conventional MR myocardial perfusion imaging is typically performed using only three short-axis slices with a temporal resolution of one RR-interval. To improve the integrated diagnostics, an acquisition and image reconstruction method based on “Multi-Slice Controlled Aliasing In Parallel Imaging Results IN Higher Acceleration (MS-CAIPIRINHA)” was developed extending anatomical coverage for MR perfusion imaging to six short-axis slices per RR-interval. MethodsAn ECG-gated radial TurboFLASH MR pulse sequence with dual band excitation was implemented on an integrated whole-body PET/MR system and a model-based reconstruction technique was developed to fully reconstruct the undersampled CAIPIRINHA acquisitions. An 18F-FDG viability PET scan was performed simultaneously to the MR protocol, additionally complemented by a late enhancement MRI acquisition (LGE). Results and conclusionThe developed imaging technique was tested in five patients with known collateralized coronary total occlusions, resulting in improved characterization of perfusion across areas of decreased tissue viability as indicated by the simultaneously determined 18F-FDG uptake. While conventional MR perfusion with only three slice positions was occasionally missing substantial parts of the viable area, the new approach achieved LV coverage only slightly inferior to LGE imaging and therefore better comparable to PET results. The quality of first-pass enhancement curves was comparable between conventional and radial MS-CAIPIRINHA-based acquisitions.

Prognostic Value of Pretreatment Radiomic Features of 18F-FDG PET in Patients With Hodgkin Lymphoma.

This study investigated whether a radiomic analysis of pretreatment F-FDG PET can predict prognosis in patients with Hodgkin lymphoma (HL). Forty-two patients who were diagnosed as having HL and underwent pretreatment F-FDG PET scans were retrospectively enrolled. For each patient, we extracted 450 radiomic features from PET images. The prognostic significance of the clinical and radiomic features was assessed in relation to progression-free survival (PFS) and overall survival (OS). Receiver operating characteristic curve, Cox proportional hazards regression, and Kaplan-Meier analyses were performed to examine the potential independent predictors and to evaluate the predictive value. Intensity nonuniformity extracted from a gray-level run-length matrix and the Ann Arbor stage were independently associated with PFS (hazard ratio [HR] = 22.8, P < 0.001; HR = 7.6, P = 0.024) and OS (HR = 14.5, P = 0.012; HR = 8.5, P = 0.048), respectively. In addition, SUV kurtosis was an independent prognosticator for PFS (HR = 6.6, P = 0.026). We devised a prognostic scoring system based on these 3 risk predictors. The proposed scoring system further improved the risk stratification of the current staging classification (P < 0.001). The radiomic feature intensity nonuniformity is an independent prognostic predictor of PFS and OS in patients with HL. We devised a prognostic scoring system, which may be more beneficial for patient risk stratification in guiding therapy compared with the current Ann Arbor staging system.

Abstract 4362: Glucose transporter 1 regulates cell glycolysis and proliferation in gastrointestinal stromal tumor and its clinicopathological significance

Abstract Background: The unique features that cancer cells prefer glycolysis rather than mitochondrial respiration despite of the presence of oxygen have been a potential target for cancer treatment. GIST is well-known as to demonstrate intense metabolic activity and avid glucose uptake on 18F-FDG PET scanning. In this study, we focused on glucose transporter 1 (GLUT 1), a key glycolytic enzyme which plays critical roles in several cancer type. The aim of this study was to examine the clinicopathological significance of GLUT1 expression in GIST and to characterize the molecular mechanism of cell glycolysis and proliferation by GIST cell. Methods: We determined the expression level of GLUT1 in 65 GIST cases, correlated those values with clinicopathological features. Furthermore, we investigated that the alteration of GLUT1 can influence on glycolysis, cell proliferation, and cell cycle distribution by extracellular flux analyzer, CCK-8 assay and flow cytometry, respectively in GIST cell in vitro. Results: Fifty-one (78.5%) cases were placed in the high GLUT1 expression group. In the high GLUT1 expression group, tumor size was significantly larger compared to the low GLUT1 expression group (P=0.02). There are significantly more high-risk cases by modified-Fletcher classification in GLUT1 expression group (P&amp;lt; 0.01). The patients with high GLUT1 expression significantly exhibited a higher SUVmax value (P&amp;lt; 0.01). Compared with the low GLUT1 expression group, the high expression group showed a significantly poorer prognosis in terms of recurrence-free survival. In vitro, GLUT1-specific siRNA suppressed cell proliferation and led to increase in G1 phase arrest. Also, knockdown of GLUT1 cells reduced glycolysis as a function of ECAR by extracellular flux analyzer. Conclusion: We showed that GLUT1 plays a critical role in GIST by regulating glycolysis and proliferation. Our study suggests that glucose transporter can be a novel target of anticancer therapeutics mediating glucose metabolism in GIST. Citation Format: Masaaki Iwatsuki, Hiroshi Sawayama, Daisuke Kuroda, Yuki Koga, Kohei Yamashita, Kazuto Harada, Shiro Iwagami, Kojiro Eto, Takatsugu Ishimoto, Yoshifumi Baba, Naoya Yoshida, Jaffer A. Ajani, Hideo Baba. Glucose transporter 1 regulates cell glycolysis and proliferation in gastrointestinal stromal tumor and its clinicopathological significance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4362.

1806-P: Improvement Brain Insulin Signaling in Antidiabetic Effect of Duodenal Jejunal Bypass Surgery

Duodenal-Jejunal bypass (DJB) can dramatically improve type 2 diabetes independent of weight loss and food restriction, while the mechanism underlying remains unclear. The most important characteristic of diabetes is hyperglycemia due to impaired glucose homeostatic regulation, increasing evidences have demonstrated that the brain can directly initiate behavioral and metabolic responses to control energy and peripheral glucose homeostasis. This study mainly focused on exploring the role of brain insulin signaling activation and brain glucose utilization in the antidiabetic mechanism of DJB. The diabetic rats that induced by Streptozotocin (STZ) injection were grouped and proceeded with DJB or Sham operation, respectively. Basal glycemic parameters, such as fasting glucose, fasting plasmid insulin, OGTT, HOMA-IR and Hb1Ac, were detected by ELISA kits. In different treated (DJB, Sham or Control) rats models, 18F-FDG PET scanning was used to detect the glucose uptake in different organs, and of the level of insulin as well as insulin signaling pathway related proteins (InsR, IRS1/2, PI3K, AKT) and glucose utilization related proteins (HK1, PFK2) was evaluated by Q-RT-PCR, Western blot or IHC in the brain. Results showed that DJB surgery significantly improved basal glycemic parameters (Blood glucose, Insulin, HOMA-IR, HbA1c and OGTT) and reversed the decreased glucose uptake in the brain which was caused by type 2 diabetes. DJB surgery not only induced the gene expression of the brain insulin as well activated the insulin related signals, but also increased the expression of glucose utilization enzymes, such as HK1 and PFK2 in the brain. These results indicated that activation of brain insulin signaling and elevation of brain glucose metabolism might play an important role in the antidiabetic effect of DJB. Disclosure Q. Yan: None. N. Li: None. R. Pan: None. H. Wang: None. B. Jiang: None. W. Wang: None. Z. Gao: None. M. Qu: None. Funding National Natural Science Foundation of China (81871892, 31671208, 81500798, 81471048); Shandong Province Natural Science Foundation (ZR2015HL128); Technology Development Plan of Weifang (2018YX027)

18F-FDG PET/CT in preoperative nodal staging of endometrial cancer: The role of radiomics to improve sensitivity in detecting nodal metastases

Objective: The introduction of SLN biopsy ultrastaging, able to identify micrometastatic deposits, increased false-negative PET/CT findings in nodal staging of endometrial cancer, as small metastatic lymph node (LN) lesions may remain undetected at visual analysis because of the limited spatial resolution of the PET technique. The aim of this study was to investigate the role of radiomics applied in women with endometrial cancer who underwent 18F-FDG PET scan, to evaluate whether imaging features computed on the primary tumor could improve sensitivity in detection of LN metastases.

Physiologic colonic fluorine-18-fluorodeoxyglucose uptake may predict response to immunotherapy in patients with metastatic melanoma.

The gut microbiota impacts response to immunotherapy in cancer patients. We sought to evaluate the role of physiologic colonic fluorine-18-fluorodeoxyglucose (F-FDG) uptake, a test that was recently shown to reflect colonic bacterial load, as a possible predictor for response to immunotherapy. We carried out a retrospective study in metastatic melanoma patients who received the immune checkpoint inhibitor ipilimumab as first-line therapy. All patients underwent an F-FDG PET scan before treatment initiation. The primary outcome was defined as response to treatment according to the RECIST criteria. Regions of interest were drawn on each transaxial slice around the outer boundaries of the colon. Uptake was measured using maximum and mean standardized uptake value (SUV). A nonparametric test was used to compare SUV between response groups. The study included 14 melanoma patients, of whom two (14.3%) achieved a complete response (CR) following treatment, eight (57.1%) achieved a partial response (PR), and four (28.6%) developed progressive disease (PD). The mean SUVmax was 1.33±0.04, 2.2±0.46, and 3.33±2.67 for individuals with CR, PR, and PD, respectively. The difference between individuals with CR and those without CR (PR or PD) in total colonic SUVmax was statistically significant (P=0.03). Thus, physiologic colonic F-FDG uptake may predict CR to immunotherapy in metastatic melanoma patients.

PET-directed combined modality therapy for gastroesophageal junction cancer: First results of the prospective MEMORI trial.

4018 Background: We evaluated a PET-guided treatment stratification for improvement in obtaining negative surgical margins (R0) in resectable gastroesophageal junction (GEJ) adenocarcinoma. According to sequential 18F-FDG PET, only 40–50% of patients (pts) respond to neoadjuvant chemotherapy (CTX). Early PET non-responders (P-NR) after induction CTX might benefit from changing to chemoradiation (CRT). Methods: 75 pts with resectable GEJ adenocarcinomas were enrolled in this interventional, prospective, non-randomized multicenter trial. Pts underwent baseline 18F-FDG PET scan followed by 1 cycle of CTX (physicians’ choice, e.g. EOX, XP, mFOLFOX6). PET was repeated at day 14-21 and responders (P-R), defined as ≥ 35% decrease in SUVmax from baseline, continued with CTX. P-NR switched to CRT (41.4 Gy/23 fractions with weekly carboplatin/paclitaxel). Pts underwent surgery 4-6 weeks post-CTX/CRT. Primary objective was an improvement of R0 resection rates in P-NR above a proportion of 70% based on results from the MUNICON1/2 trials. Secondary endpoints include disease-free survival (DFS), overall survival (OS), measured from randomization to death from any cause, and translational endpoints. Results: Between 12/2014 and 07/ 2018 160 pts with resectable GEJ adenocarcinomas were prospectively screened with PET in three German university centers. Overall, 85 pts (53%) could not be included due to previously undetectable metastases (40/25%), no or too low FDG uptake of the primary tumor (21/13%), other reasons (24/15%). 75 eligible pts were enrolled in the study and 69 were evaluable. Based on PET criteria, 47 (68%) and 22 (32%) were P-R and P-NR, respectively. R0 resection rates were 94% (44/47) for P-R and 91% (20/22) for P-NR. Pathologic complete remission (pCR; &lt; 10% vital tumor cells), was 33% (15/46) in P-R and 55% (12/22) in P-NR. With a median follow-up time of 19 months (mo), estimated 18 mo DFS was 71%/61% for P-R/P-NR, respectively. Observed median 18 mo OS was 95% for P-R and 75% for P-NR. Conclusions: Alternative CRT for GEJ adenocarcinoma improved R0- and pCR rates among pts who were P-NR after induction CTX. PET response was prognostic for a prolonged OS and DFS. Clinical trial information: 2014-000860-16.

Mild Cognitive Impairment with a High Risk of Progression to Alzheimer's Disease Dementia (MCI-HR-AD): Effect of Souvenaid® Treatment on Cognition and 18F-FDG PET Scans.

Background:Previous studies have shown that Souvenaid (medical food) can have benefits on memory, cognition, and function in early Alzheimer’s disease (AD) and mild cognitive impairment (MCI).Objective:Demonstrate that Souvenaid could improve or maintain cognition and has an effect on neurodegeneration biomarkers.Methods:This cohort study was carried out from June 2015 through December 2016 in the Neurology Department, Infanta Cristina Hospital, Madrid, Spain. MCI-HR-AD were recruited using Petersen criteria, neuropsychology (NPS), and 18F-FDG PET scans to confirm the high risk of progression to dementia with one year of follow-up. Age, sex, vascular risk factors (VRF), and NPS values (Barcelona brief version) were analyzed. 18F-FDG PET scans were analyzed as a visual procedure. The study was approved by the Research Committee of ICH. Statistical analysis was made with SPSS 22.0 version.Results:Subjects included 43 MCI patients (58.5% women; mean age 69.78±7.89): 17 receiving Souvenaid® treatment (ST), 24 receiving no treatment (WT) and 2 who withdrew. No differences were seen in VRF, only hypercholesterolemia, and were less prevalent in the ST group (p = 0.002). The rate of progression to dementia was 48.8% (no differences between groups, p = 0.654). A second round of 18F-FDG PET scans showed a significance worsening of glucose metabolism in WT (p = 0.001) versus ST, in which it was low (p = 0.050). For NPS testing, there was a significant worsening in memory performance in the WT group (p = 0.011) and a stabilization in ST (p = 0.083), as well as in executive functions and attention (worsening in WT, p = 0.014). For the Subjective Changing Scale (SCS), caregivers indicated a stabilization/improvement in ST (p = 0.017).Conclusion:Souvenaid had a significant effect on several cognitive domains, and on SCS in patients with MCI-HR-AD. Its intervention had an impact on preservation on 18F-FDG PET scans.

Tumour necrosis as assessed with 18F-FDG PET is a potential prognostic marker in diffuse large B cell lymphoma independent of MYC rearrangements

ObjectivesMYC gene rearrangements in diffuse large B cell lymphomas (DLBCLs) result in high proliferation rates and are associated with a poor prognosis. Strong proliferation is associated with high metabolic demand and tumour necrosis. The aim of this study was to investigate differences in the presence of necrosis and semiquantitative 18F-FDG PET metrics between DLBCL cases with or without a MYC rearrangement. The prognostic impact of necrosis and semiquantitative 18F-FDG PET parameters was investigated in an explorative survival analysis.MethodsFluorescence in situ hybridisation analysis for MYC rearrangements, visual assesment, semiquantitative analysis of 18F-FDG PET scans and patient survival analysis were performed in 61 DLBCL patients, treated at a single referral hospital between 2008 and 2015.ResultsOf 61 tumours, 21 (34%) had a MYC rearrangement (MYC+). MYC status was neither associated with the presence of necrosis on 18F-FDG PET scans (necrosisPET; p = 1.0) nor associated with the investigated semiquantitative parameters maximum standard uptake value (SUVmax; p = 0.43), single highest SUVmax (p = 0.49), metabolic active tumour volume (MATV; p = 0.68) or total lesion glycolysis (TLG; p = 0.62). A multivariate patient survival analysis of the entire cohort showed necrosisPET as an independent prognostic marker for disease-specific survival (DSS) (HR = 13.9; 95% CI 3.0–65; p = 0.001).ConclusionsMYC rearrangements in DLBCL have no influence on the visual parameter necrosisPET or the semi-quantiative parameters SUVmax, MATV and TLG. Irrespective of MYC rearrangements, necrosisPET is an independent, adverse prognostic factor for DSS.Key Points• Retrospective analysis indicates that MYC rearrangement is not associated with necrosis on18F-FDG PET (necrosisPET) scans or semiquantitative18F-FDG PET parameters.• NecrosisPETis a potential independent adverse prognostic factor for disease-specific survival in patients with DLBCL and is not influenced by the presence of MYC rearrangements.

Combination of breast imaging parameters obtained from 18F-FDG PET and CT scan can improve the prediction of breast-conserving surgery after neoadjuvant chemotherapy in luminal/HER2-negative breast cancer

IntroductionThe luminal/Human Epidermal growth factor Receptor 2 (HER2) negative subtype of breast cancer has low chemo-sensitivity. When neoadjuvant chemotherapy (NAC) is indicated in this subtype, before a possible breast-conserving surgery (BCS), it is more reasonable to target tumor shrinkage than complete pathological tumor response. We aimed to identify breast and tumor 18Fluoro-deoxy-glucose (18F-FDG) PET-CT scan imaging features for the early prediction of BCS after NAC in luminal/HER2 negative subtypes of breast cancer. Material and methodsSeventy-seven consecutive women with luminal/HER2-negative breast cancer for whom BCS was initially not feasible and NAC was prescribed, to decrease tumor size before surgery, were included retrospectively. An 18F-FDG PET-CT scan exam was performed before and after the first course of NAC. ResultsAfter NAC, 36% (28/77) of women had a mastectomy and 64% (49/77) underwent BCS. Patients with a mastectomy had lower total breast volume (BVtotal) (p = 0.002), lower decrease in Δmetabolic tumor volume (ΔMTV) (p = 0.03) and lower SUVmax2 (p = 0.05). Using ROC Curve analyses to define the optimal predictive threshold of BVtotal (496 cm3) and ΔMTV (-17.1%), 3 subgroups of women with different odds of BCS after treatment were identified (p = 0.001): low, medium and high probability groups (respectively 29%, 62% and 82%). ConclusionsFor patients with Luminal/HER2 negative breast cancer, the combination of the imaging features of the tumor and the mammary gland, obtained with 18F-FDG PET-CT at baseline and after the first cycle of NAC, may allow the physician to evaluate the probability of BCS.

18F-FDG positron emission tomography as a novel diagnostic tool for peripheral nerve injury

BackgroundGlucose hypermetabolism in denervated skeletal muscle suggests the potential for developing a diagnostic tool for peripheral nerve injuries. Herein, we investigated the characteristics and molecular mechanism of this phenomenon. New methodTemporal course of glucose hypermetabolism and development of abnormal spontaneous activities (ASA) through electromyography (EMG) were investigated in rats with complete sciatic nerve injuries. Rats with partial sciatic nerve injuries were used to investigate the relationship between nerve injury severity and change in glucose metabolism. Rapamycin-treated rats were used to study molecular mechanism. Mean lesion-to-normal count ratios (LNRmean) was calculated as a numeric value of the 18F-FDG uptake. ResultsGlucose hypermetabolism began 2 days after nerve injury and lasted up to 12 weeks, with the maximum increase at 1 week after denervation (10-fold increase compared to sham-operated muscle; LNRmean, sham, 1.360 ± 0.452; denervation, 10.340 ± 4.094; n = 5; P < 0.05). The metabolic changes showed similar temporal characteristics to ASA on EMG. The signal intensity of 18F-FDG uptake in denervated skeletal muscle was strongly related to nerve injury severity in a partial nerve injury model (Pearson correlation coefficient 0.63, P < 0.05). Suppression of mTOR by rapamycin treatment reduced the increase in peak glucose hypermetabolism in muscle denervation. Comparison with existing methodMetabolic changes in 18F-FDG PET scans have a wider time span than abnormalities on EMG after denervation and it is correlated with the severity of nerve injury assessed by NCS. Conclusions18F-FDG PET may be used to diagnose and evaluate peripheral nerve injuries.

Gender-disease interaction on brain cerebral metabolism in cancer patients with depressive symptoms

BackgroundCancer patients are accompanied with high morbidity of depression, and gender effects are known to inhabit in the depressive episodes. This study aimed to explore the gender effects in cancer patients, and the relationship between gender-cancer factors and the depression symptoms.MethodsThe 18F-FDG PET scans of 49 cancer patients and 48 normal controls were included. We used voxel-wise analysis to explore the effects of cancer factor and gender factor in cerebral glucose metabolism. Beck Depression Inventory was utilized to quantify the depression symptoms in cancer patients.ResultsOur results showed significant cancer main effects primarily in superior frontal gyrus and parietal gyrus; and significant gender main effects primarily in cerebellum posterior lobe, inferior temporal gyrus. Significant gender-by-cancer interaction effects were also observed, which primarily located in superior frontal gyrus. We showed the metabolic intensities of the 5 aforementioned clusters were related to the mental stress of depressive emotion.ConclusionsOur results suggested that males and females have different psychological endurance when facing cancer diagnosis or preventing depression. Furthermore, the cerebral abnormal metabolism might serve as a depressive indicator for cancer patients. The present findings provided supporting evidence for abnormal cerebral glucose metabolism affected by gender factor in cancer patients with mental stress of depressive emotion, and these brain regions should be concerned in clinic.

PET-CT has low specificity for mediastinal staging of non-small-cell lung cancer in an endemic area for tuberculosis: a diagnostic test study (LACOG 0114)

BackgroundThe present study aims to assess the performance of 18F-FDG PET-CT on mediastinal staging of non-small cell lung cancer (NSCLC) in a location with endemic granulomatous infectious disease.MethodsDiagnostic test study including patients aged 18 years or older with operable stage I-III NSCLC and indication for a mediastinal lymph node biopsy. All patients underwent a 18F-FDG PET-scan before invasive mediastinal staging, either through mediastinoscopy or thoracotomy, which was considered the gold-standard. Surgeons and pathologists were blinded for scan results. Primary endpoint was to evaluate sensitivity, specificity and positive and negative predictive values of PET-CT with images acquired in the 1st hour of the exam protocol, using predefined cutoffs of maximal SUV, on per-patient basis.ResultsOverall, 85 patients with operable NSCLC underwent PET-CT scan followed by invasive mediastinal staging. Mean age was 65 years, 49 patients were male and 68 were white. One patient presented with active tuberculosis and none had HIV infection. Using any SUV_max > 0 as qualitative criteria for positivity, sensitivity and specificity were 0.87 and 0.45, respectively. Nevertheless, even when the highest SUV cut-off was used (SUV_max ≥5), specificity remained low (0.79), with an estimated positive predictive value of 54%.ConclusionsOur findings are in line with the most recent publications and guidelines, which recommend that PET-CT must not be solely used as a tool to mediastinal staging, even in a region with high burden of tuberculosis.Trial registrationThe LACOG 0114 study was registered at ClinicalTrials.gov, before study initiation, under identifier NCT02664792.

Principal Components Analysis of Brain Metabolism Predicts Development of Alzheimer Dementia.

The value of 18F-FDG PET for predicting conversion from mild cognitive impairment (MCI) to Alzheimer dementia (AD) is currently under debate. We used a principal components analysis (PCA) to identify a metabolic AD conversion-related pattern (ADCRP) and investigated the prognostic value of the resulting pattern expression score (PES). Methods:18F-FDG PET scans of 544 MCI patients were obtained from the Alzheimer Disease Neuroimaging Initiative database and analyzed. We implemented voxel-based PCA and standard Statistical Parametric Mapping analysis (as a reference) to disclose cerebral metabolic patterns associated with conversion from MCI to AD. By Cox proportional hazards regression, we examined the prognostic value of candidate predictors. Also, we constructed prognostic models with clinical, imaging, and clinical and imaging variables in combination. Results: PCA revealed an ADCRP that involved regions with relative decreases in metabolism (temporoparietal, frontal, posterior cingulate, and precuneus cortices) and relative increases in metabolism (sensorimotor and occipital cortices, cerebellum, and left putamen). Among the predictor variables age, sex, Functional Activities Questionnaire, Mini-Mental State Examination, apolipoprotein E, PES, and normalized 18F-FDG uptake (regions with significant hypo- and hypermetabolism in patients with conversion vs. those without conversion), PES was the best independent predictor of conversion (hazard ratio, 1.77, per z score increase; 95% CI, 1.24-2.52; P < 0.001). Moreover, adding PES to the model including the clinical variables significantly increased its prognostic value. Conclusion: The ADCRP expression score was a valid predictor of conversion. A combination of clinical variables and PES yielded a higher accuracy than each single tool in predicting conversion from MCI to AD, underlining the incremental utility of 18F-FDG PET.

Brain metabolism and related connectivity in patients with acrophobia treated by virtual reality therapy: an 18F-FDG PET pilot study sensitized by virtual exposure

BackgroundThe aim of this pilot study is to investigate the impact of virtual reality exposure therapy (VRET) on brain metabolism and connectivity.Eighteen patients with acrophobia were assessed by an 18F-FDG PET scan sensitized by virtual exposure before treatment, and nine of them were assessed again after eight sessions of VRET. Statistical Parametric Mapping was used to study the correlations between metabolism and pretherapeutic clinical scores and to compare metabolism before and after VRET (p voxel < 0.005, corrected for cluster volume). Metabolic connectivity was evaluated through interregional correlation analysis.ResultsBefore therapy, a positive correlation was found between scores on the behavioural avoidance test and left occipital metabolism (BA17-18). After VRET, patients presented increased metabolism in the left frontal superior gyri and the left precentral gyrus, which showed increased metabolic connectivity with bilateral occipital areas (BA17-18-19), concomitant with clinical recovery.ConclusionsThis study highlights the exciting opportunity to use brain PET imaging to investigate metabolism during virtual exposure and reports the involvement of the visual-motor control system in the treatment of acrophobia by VRET.

Automatic localization of normal active organs in 3D PET scans

PET imaging captures the metabolic activity of tissues and is commonly visually interpreted by clinicians for detecting cancer, assessing tumor progression, and evaluating response to treatment. To automate accomplishing these tasks, it is important to distinguish between normal active organs and activity due to abnormal tumor growth. In this paper, we propose a deep learning method to localize and detect normal active organs visible in a 3D PET scan field-of-view. Our method adapts the deep network architecture of YOLO to detect multiple organs in 2D slices and aggregates the results to produce semantically labeled 3D bounding boxes. We evaluate our method on 479 18F-FDG PET scans of 156 patients achieving an average organ detection precision of 75–98%, recall of 94–100%, average bounding box centroid localization error of less than 14 mm, wall localization error of less than 24 mm and a mean IOU of up to 72%.

Comparison of 99mTc-methyl diphosphonate bone scintigraphy and 18F-fluorodeoxyglucose positron emission tomography/computed tomography to predict histologic response to neoadjuvant chemotherapy in patients with osteosarcoma

We compared the usefulness of 99mTc-methyl diphosphonate (99mTc-MDP) bone scintigraphy and 18F-fluorodeoxyglucose (FDG) for positron emission tomography/computed tomography (PET/CT) in predicting histologic response in patients with osteosarcoma receiving neoadjuvant chemotherapy (NAC).We retrospectively reviewed 62 patients with high-grade osteosarcoma who had received 2 cycles of NAC and surgery. All patients underwent 99mTc-MDP bone scintigraphy and 18F-FDG PET/CT before and after NAC. 99mTc-MDP uptake in the primary tumor was measured quantitatively as the maximum tumor-to-nontumor ratio (T/NTmax) and 18F-FDG uptake was measured as the maximum standardized uptake value (SUVmax), before and after NAC. The percent changes of T/NTmax (percent changes of the maximum tumor-to-nontumor ratio [Δ%T/NTmax]) and SUVmax (percent changes of the maximum standardized uptake value [Δ%SUVmax]) after NAC were calculated and the correlations between these parameters were evaluated. After surgery, the effects of NAC were graded histopathologically (good vs poor) and the optimum cut-off values of Δ%T/NTmax and Δ%SUVmax for predicting histologic response were assessed using the receiver operating characteristic (ROC) curve analysis.Δ%T/NTmax and Δ%SUVmax were positively correlated with each other (r = 0.494, P < .01). Based on the ROC curve analysis, both Δ%T/NTmax (area under the curve [AUC] = .772, P < .01) and Δ%SUVmax (AUC = .829, P < .01) predicted good histologic response. However, there was no significant difference between the AUCs of Δ%T/NTmax and Δ%SUVmax (P = .44). The sensitivity and specificity for predicting good histologic response were 83.3% and 75.0%, for the criterion Δ%T/NTmax <–12.5%, and 80.0% and 81.3% for the criterion Δ%SUVmax <−49.0%, respectively.The 99mTc-MDP bone scan and 18F-FDG PET scan are non-inferior to each other in predicting the histologic response of osteosarcoma treatments. The 99mTc-MDP bone scan and 18F-FDG PET scan showed respective advantages with differing features. Therefore, physicians should consider which scan is appropriate for their own institute based on the advantages of each scan and the circumstances of the institute.

Influence of age on radiomic features in 18F-FDG PET in normal breast tissue and in breast cancer tumors

BackgroundTo help interpret measurements in breast tissue and breast tumors from 18F-FDG PET scans, we studied the influence of age in measurements of PET parameters in normal breast tissue and in a breast cancer (BC) population.Results522 women were included: 331 pts without history of BC (B-VOI) and 191 patients with BC (T-VOI). In B-VOI, there were significant differences between all age groups for Standardized Uptake Values (SUVs) and for 12 textural indices (TI) whereas histogram-based indices (HBI) did not vary between age groups. SUV values decreased over time whereas Homogeneity increased. We had a total of 210 T-VOI and no significant differences were found according to the histological type between 190 ductal carcinoma and 18 lobular carcinoma. Conversely, according to BC subtype most differences in PET parameters between age groups were found in Triple-Negative tumors (52) for 9 TI. On post-hoc Hochberg, most differences were found between the <45 year old (PRE) group and POST groups in NBT and in Triple-Negative tumors.ConclusionWe found significant SUVs and TI differences as a function of age in normal breast tissue and in BC radiomic phenotype with Triple-Negative tumors being the most affected. Our findings suggest that age should be taken into account as a co-covariable in radiomic models.MethodsPatients were classified in 3 age groups: <45 yo (PRE), ≥45 and <55 yo (PERI) and ≥55 and <85 yo (POST) and we compared PET parameters using Anova test with post-hoc Bonferroni/Hochberg analyses: SUV (max, mean and peak), HBI and TI in both breasts and in breast tumor regions.

Oligometastatic Prostate Cancer: Molecular Imaging and Clinical Management Implications in the Era of Precision Oncology.

1338 Objectives: Differentiated thyroid cancer (DTC) patients with elevated or rising serum thyroglobulin (Tg) levels and multiple other negative conventional imaging studies represent a clinically difficult group of patients. 99m Tc-sestamibi is a non-conventional imaging study for DTC that was used in the 1980s-1990s to help evaluate DTC patients before being replaced with 18F-FDG. However, 18F-FDG PET scans may also be negative in these patients. This is a preliminary analysis of our study to evaluate the diagnostic use of 99mTc-sestamibi scans to identify the source of elevated or rising Tgs in patients with negative conventional imaging including negative 18F-FDG PET scans. Methods This prospective study included DTC patients who were at least 18 years old, had at least one prior 131I therapy, and had elevated Tg>5 ng/ml or positive anti-Tg antibodies (TgAb). In addition, all of the following imaging studies must have been clinically reported as negative for recurrence or metastasis within the last 12 months: neck ultrasound, diagnostic radioiodine scan, chest x-ray, CT of the chest/abdomen with/without contrast, and 18F-FDG PET/CT. If other imaging studies were performed, such as bone scans or brain imaging, these must also have been read as negative. This study was approved by the IRB at MedStar Health and all participants signed informed consent. Participants were injected with 925 MBq (25 mCi) of 99mTc-sestamibi intravenously and whole body images were acquired after ~1h with acquisition speed 4cm/min with parallel-hole low-energy collimator. Extra spot view, pinhole view, or SPECT/CT images were performed when necessary. Two blinded nuclear medicine physicians independently interpreted the 99mTc-sestamibi images, and graded each foci 1-5 (1 = definite physiological uptake or artifact; 2 = most likely physiological uptake or artifact; 3 = indeterminate; 4 = most likely recurrence or metastasis; 5 = definite recurrence or metastasis). Discordant findings were resolved by consensus. Foci graded 3-5 were categorized as positive result and was followed-up for confirmation. Results A total of four patients completed the sestamibi scan to date. One out of four patients (Patient1) was positive on the sestamibi scan for distant metastasis. In Patient 1, the sestamibi whole-body posterior image demonstrated abnormal focal uptake in the right posterior calvarium and corresponding to an occipital lytic bone lesion on the SPECT/CT (Figure 1). The patient underwent surgical resection of the skull metastasis, and pathology confirmed metastatic thyroid cancer. Five months post-surgery the suppressed Tg was markedly reduced and stable at ~3.2ng/ml. Table 1 shows the sestamibi scan results, subsequent management and follow-up. With confirmation of the location of the metastatic foci in Patient 1, the two negative 18F-FDG PET/CT that were previously performed one year apart were reviewed again. The radiology reports did not document interpretation of the low-dose localization CT. In retrospect, the lytic skull metastasis was visible on both of the head CT, but could have been easily missed on the PET due to the normal intensive brain 18F-FDG activity. Conclusions In this preliminary analysis, 99mTc-sestamibi was able to identify the source of elevated Tg levels in one out of four DTC patients with biochemical recurrence and negative conventional imaging studies. 99mTc-sestamibi may have a role in thyroid cancer localization when physical exam, neck ultrasound, radioiodine scan, chest/abdomen CT, and 18F-FDG PET/CT could not identify. Additional patients are being recruited. Research Support We are grateful for the generous donations from our patients.