PSMA-Hornet: Fully-automated, multi-target segmentation of healthy organs in PSMA PET/CT images.

BACKGROUND: Prostate-specific membrane antigen (PSMA) PET imaging represents a valuable source of information reflecting disease stage, response rate, and treatment optimization options, particularly with PSMA radioligand therapy. Quantification of radiopharmaceutical uptake in healthy organs from PSMA images has the potential to minimize toxicity by extrapolation of the radiation dose delivery towards personalization of therapy. However, segmentation and quantification of uptake in organs requires labor-intensive organ delineations that are often not feasible in the clinic nor scalable for large clinical trials. PURPOSE: In this work we develop and test the PSMA Healthy organ segmentation network (PSMA-Hornet), a fully-automated deep neural net for simultaneous segmentation of 14 healthy organs representing the normal biodistribution of [18 F]DCFPyL on PET/CT images. We also propose a modified U-net architecture, a self-supervised pre-training method for PET/CT images, a multi-target Dice loss, and multi-target batch balancing to effectively train PSMA-Hornet and similar networks. METHODS: The study used manually-segmented [18 F]DCFPyL PET/CT images from 100 subjects, and 526 similar images without segmentations. The unsegmented images were used for self-supervised model pretraining. For supervised training, Monte-Carlo cross-validation was used to evaluate the network performance, with 85 subjects in each trial reserved for model training, 5 for validation, and 10 for testing. Image segmentation and quantification metrics were evaluated on the test folds with respect to manual segmentations by a nuclear medicine physician, and compared to inter-rater agreement. The model's segmentation performance was also evaluated on a separate set of 19 images with high tumor load. RESULTS: With our best model, the lowest mean Dice coefficient on the test set was 0.826 for the sublingual gland, and the highest was 0.964 for liver. The highest mean error in tracer uptake quantification was 13.9% in the sublingual gland. Self-supervised pretraining improved training convergence, train-to-test generalization, and segmentation quality. In addition, we found that a multi-target network produced significantly higher segmentation accuracy than single-organ networks. CONCLUSIONS: The developed network can be used to automatically obtain high-quality organ segmentations for PSMA image analysis tasks. It can be used to reproducibly extract imaging data, and holds promise for clinical applications such as personalized radiation dosimetry and improved radioligand therapy.

The Elusive Neuroendocrine Tumor: Finding the Ectopic ACTH Source 16 Years After the Diagnosis of Cushing Syndrome.

Ectopic adrenocorticotropin hormone (ACTH) syndrome (EAS) accounts for the minority of cases of Cushing syndrome. Up to 20% of these cases remain occult, despite multiple imaging attempts to localize the ACTH-producing tumor. Here we describe long-term follow-up of a 41-year-old woman, with ectopic Cushing syndrome initially classified as occult due to negative localization studies, who had bilateral adrenalectomy to manage hypercortisolism. After 16 years and many computed tomography (CT) scans, magnetic resonance imaging scans, Octreoscans, and 2 exploration surgeries for false positives on imaging, the source of ectopic ACTH production was localized in the pancreas utilizing molecular imaging with gallium-68 somatostatin receptor-targeted positron emission tomography (PET)/CT and fluorine-18 fluorodeoxyglucose PET/CT. She underwent a distal pancreatectomy, and pathology confirmed a 1.7-cm well-differentiated pancreatic neuroendocrine tumor with a moderately strong reactivity to ACTH stain. This case demonstrates the utility of multiple functional imaging modalities in resolving these "cold cases" of occult ectopic Cushing syndrome and the importance of a timely management of hypercortisolism with bilateral adrenalectomy.

Comparing digital to analog prostate-specific membrane antigen-targeted piflufolastat 18 F PET/CT in prostate cancer patients in early biochemical failure.

PURPOSE: Prostate-specific membrane antigen (PSMA) positron emission tomography/computer tomography (PET/CT) in prostate cancer patients with biochemical failure(BCF) showslimited sensitivity when the prostate-specific antigen(PSA) <0.5 ng/mL. The development of digital PET/CT has greatly improved smaller lesion detection. This study's goal was to compare the performance and clinical value of PSMA-targeted piflufolastat PET/CT for prostate cancer BCF with digital versus analog PET/CT. METHODS: In this retrospective study, all piflufolastat PET/CT scans in subjects with PSA ≤ 3.0 ng/mL who were referred for prostate cancer BCF were included. The performance characteristics of 171 analog PET/CT studies in 155 subjects from May 2017 to January 2020 and 106 digital PET/CT studies in 103 subjects from February 2020 to December 2020 were compared. Lesions were considered malignant if they did not match the known physiological distribution of piflufolastat and did not represent uptake in benign lesions. PSMA PET/CT studies were considered positive if at least one malignant lesion was detected and negative if none were detected. RESULTS: Digital piflufolastat PET/CT outperformed analog piflufolastat PET/CT in subjects with PSA < 0.5 ng/mL with a positivity rate of 69% versus 37%, respectively. In patients with PSA ≥ 0.5 ng/mL, both technologies performed similarly. There was no statistically significant difference between the number or size of piflufolastat-avid lesions detected per PET/CT study. CONCLUSION: In prostate cancer patients with BCF and PSA < 0.5 ng/mL, digital piflufolastat PET/CT has a higher detection rate of malignant lesions than analog piflufolastat PET/CT.

Blinded Clinical Evaluation for Dementia of Alzheimer's Type Classification Using FDG-PET: A Comparison Between Feature-Engineered and Non-Feature-Engineered Machine Learning Methods.

BACKGROUND: Advanced machine learning methods can aid in the identification of dementia risk using neuroimaging-derived features including FDG-PET. However, to enable the translation of these methods and test their usefulness in clinical practice, it is crucial to conduct independent validation on real clinical samples, which has yet to be properly delineated in the current literature. OBJECTIVE: In this paper, we present our efforts to enable such clinical translational through the evaluation and comparison of two machine-learning methods for discrimination between dementia of Alzheimer's type (DAT) and Non-DAT controls. METHODS: FDG-PET-based dementia scores were generated on an independent clinical sample whose clinical diagnosis was blinded to the algorithm designers. A feature-engineered approach (multi-kernel probability classifier) and a non-feature-engineered approach (3D convolutional neural network) were analyzed. Both classifiers were pre-trained on cognitively normal subjects as well as subjects with DAT. These two methods provided a probabilistic dementia score for this previously unseen clinical data. Performance of the algorithms were compared against ground-truth dementia rating assessed by experienced nuclear physicians. RESULTS: Blinded clinical evaluation on both classifiers showed good separation between the cognitively normal subjects and the patients diagnosed with DAT. The non-feature-engineered dementia score showed higher sensitivity among subjects whose diagnosis was in agreement between the machine-learning models, while the feature-engineered approach showed higher specificity in non-consensus cases. CONCLUSION: In this study, we demonstrated blinded evaluation using data from an independent clinical sample for assessing the performance in DAT classification models in a clinical setting. Our results showed good generalizability for two machine-learning approaches, marking an important step for the translation of pre-trained machine-learning models into clinical practice.

Diagnostic performance of 18F-DCFPyL positron emission tomography/computed tomography for biochemically recurrent prostate cancer and change-of-management analysis.

INTRODUCTION: Conventional imaging (CI) performs poorly to identify sites of disease in biochemically recurrent prostate cancer. 68Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) is most studied but has a very short half-life. This study reports the diagnostic performance of the novel prostate-specific membrane antigen (PSMA) radiotracer 18F-DCFPyL using real-life data and tumor board simulation to estimate the impact of 18F-DCFPyL PET on patient management. METHODS: Ninety-three 18F-DCFPyL PET/CT scans performed for patients previously treated for prostate cancer with a rising prostate-specific antigen (PSA) were retrospectively compared to contemporary CI and clinical imaging and PSA followups. A chart review was performed to document prior imaging, pathology results, serial serum PSA measurements, and other pertinent clinical data. Clinical utility of 18F-DCFPyL PET was measured using a simulated tumor board formed by three physicians with extensive prostate cancer experience deciding on management with and without knowledge of PET/CT results. RESULTS: At median PSA 2.27 (interquartile rage [IQR] 5.27], 82% of 18F-DCFPyL PET/CT demonstrated at least one site of disease: non-regional lymph nodes (37% of scans), regional lymph node metastases (28%), local recurrence (27%), and bone metastases (20%), with higher PET positivity at higher PSA. Compared to 18F-DCFPyL PET/CT, CI showed overall poor performance, with accuracy below 20% for all extent of disease. PET/CT changed management in 44% of cases. The most frequent scenario was a radical change from initiating androgen deprivation therapy (ADT) to stereotactic body radiotherapy (SBRT) of oligo-lesional disease. In univariate and multivariate analysis, no patient characteristic could predict change of management by PET/CT results. CONCLUSIONS: 18F-DCFPyL significantly outperforms CI in recurring prostate cancer and is likely to impact management.

Ureteral Metastasis From Prostate Cancer: A PSMA PET Pitfall.

A 72-year-old man with a history of prostate adenocarcinoma initially managed by radical prostatectomy and salvage radiation therapy underwent resection of a left vas deferens recurrence identified on PSMA PET. Despite an initial response, PSA failed to fall below 3.5 ng/L, prompting re-evaluation with PSMA PET/CT: a left distal hydroureter with presumed physiologic urine activity remains despite diuretic administration. Upon scrutiny of the prior PSMA PET/CT and diagnostic CTs, the distal ureteral uptake matched a subtle circumferential area of enhancing mild ureteral thickening. Pathological review after left uretectomy confirmed metastatic prostate cancer.

Splenic Hemangioma as a Potential Pitfall on PSMA-Targeted 18F-DCFPyL PET/CT.

A 69-year-old man with biochemical recurrence after radical prostatectomy underwent 6 months of androgen deprivation therapy. Upon discontinuation of androgen deprivation therapy, serum prostate-specific antigen rose again to 0.69 ng/mL, and F-DCFPyL PET/CT was performed to identify the site of recurrence. However, only an intense focus of uptake in the spleen could be found. Subsequent contrast-enhanced MRI findings were pathognomonic for splenic hemangioma.

Incidental Hydroxyapatite Ocular Implant Uptake on Bone Scan Done for Prostate Cancer Staging: Case Report and Brief Review

A 74-year-old man recently diagnosed with high-risk prostate cancer with high serum prostate specific antigen was referred to nuclear medicine for a technetium-99m-methylene diphosphonate (Tc-99m MDP) bone scan. On delayed three-hour anterior planar image, an unexpected round focus of intense uptake was found overlying the right orbit. Single-photon emission computed tomography/computed tomography localized the uptake to an ocular prosthesis. The hydroxyapatite composition of the ocular implant can be recognized by its bone-like density and its intense accumulation of Tc-99m MDP. Review of the patient's history revealed remote right eye evisceration secondary to a complication of cataract surgery, consistent with the findings.

18F-fluorodeoxyglucose positron emission tomography/computed tomography in extensive bland portal vein thrombosis from retroperitoneal adenocarcinoma.

A 73-year-old woman undergoing hormone therapy for previously treated localized breast cancer presented at oncology follow-up 4 years after mastectomy/radiation therapy with weight loss, night sweats, and abdominal pain. Contrast computed tomography (CT) abdomen revealed a soft-tissue mass posterior to the pancreas, several enlarged retroperitoneal lymph nodes, and a dilated portal vein. On 18F-fluorodeoxyglucose positron emission tomography/CT, metabolic activity extended along the portal vein, outlining most of the liver venous system. This "tree-like" appearance was diagnostic of recent portal vein thrombosis by vascular compression from the retroperitoneal mass. Biopsy of the mass later confirmed undifferentiated adenocarcinoma without breast cancer marker expression.

18F-fluorocholine positron emission tomography-computed tomography (18F-FCH PET/CT) for staging of high-risk prostate cancer patients.

INTRODUCTION: We sought to evaluate the diagnostic performance of 18F-fluorocholine positron emission tomography-computed tomography (18F-FCH PET/CT) for initial staging of patients with high-risk prostate cancer. Secondary objectives were to compare the value of 18F-FCH PET/CT to conventional imaging modalities and to evaluate its clinical impact. METHODS: We conducted a retrospective study of 76 patients who underwent 18F-FCH PET/CT for initial staging of high-risk prostate cancer. Using pre-established validation criteria, sensitivity and specificity were determined for metastatic disease. Results were compared to findings on magnetic resonance imaging (MRI), computed tomography (CT), and bone scan (BS) when available. RESULTS: Twenty-two (29%) PET/CT scans were positive, 49 (64%) negative, and five (7%) equivocal for nodal or metastatic disease. Of the positive scans, 17 showed regional lymph node involvement, 12 distant nodes, five bone metastases, and three lung metastases. Overall per-patient sensitivity, specificity, positive and negative predictive values for metastatic disease were 65%, 100%, 100%, and 78%, respectively. Sensitivity, specificity, and positive and negative predictive values were 64%, 100%, 100%, and 80%, respectively, for nodal involvement and 86%, 100%, 100%, and 98%, respectively, for bone and other metastases. Conventional imaging was negative for the lesion(s) found on PET/CT in five patients. PET/CT changed the clinical management in nine patients (12%). CONCLUSIONS: Although 18F-FCH PET/CT offers some benefits over conventional imaging and demonstrates a high specificity, it remains limited by its sensitivity in the context of high-risk prostate cancer staging. PET with novel urea-based small molecule prostate-specific membrane antigen (PSMA) inhibitors may overcome some of these limitations. However, the interpretation of the study result is limited by the lack of available histological gold standard, the inclusion of several patients who received androgen-deprivation therapy (ADT) prior to PET/CT, our retrospective design, and a relatively small sample size.

The Role of FDG PET in Diabetic Myonecrosis: A Rare and Underrecognized Complication of Diabetes.

A 66-year-old man with poorly controlled type 2 diabetes was admitted for acute bilateral calf pain in the context of coronary artery disease, chronic renal failure, and peripheral neuropathy. Lower-extremity Doppler ultrasound excluded deep vein thrombosis. FDG-PET was performed to exclude a suspected infection because of elevated white blood cells and inflammatory markers but normal creatinine kinase levels. PET scan demonstrated intense bilateral calf muscle and left thigh muscle uptake, which in combination with the patient's history was consistent with diabetic myonecrosis, a rare end-stage complication of diabetes. The patient was managed conservatively, and pain resolved following a typical self-limited course.

Small Lymph Node Metastasis Detected by 68Ga-Prostate-Specific Membrane Antigen But Not 18F-Fluciclovine PET/CT in Low-Prostate-Specific Antigen Biochemical Recurrence of Prostate Cancer.

A 58-year-old man with Gleason 4+3 prostate cancer was initially treated by radical prostatectomy followed by salvage radiotherapy to the prostate bed for postoperative biochemical failure. One year later, F-fluorocholine PET/CT detected a pelvic lymph node recurrence, which was treated with radiation therapy and 6 months of androgen deprivation. PSA started to rise again 18 months later, but F-fluciclovine PET/CT failed to demonstrate the site of recurrence at a PSA of 0.63 ng/mL. However, Ga-PSMA PET/CT revealed a single positive 4-mm perirectal lymph node (PSA 0.80 ng/mL at time of scan), in retrospect anatomically apparent but negative on F-fluciclovine PET/CT.

I-131 Radiation-Induced Myelosuppression in Differentiated Thyroid Cancer Therapy.

Radioactive iodine (RAI) treatment of differentiated thyroid cancer has been used in clinical practice for almost 60 years and is generally accepted to be a safe and efficacious treatment. Severe toxicity in the form of radiation pneumonitis, sometimes progressing to fibrosis, and bone marrow suppression are reported but remain rare. We present a case of severe myelosuppression requiring hospitalization and transfusion support in an otherwise well, young female patient who had received 175 mCi I-131 for low-volume micronodular lung disease one month prior, with a cumulative lifetime administered activity of 575 mCi. The most important risk factors for myelosuppression following RAI are the activity received, the amount of functioning thyroid tissue present, and the lifetime cumulative activity received.

Asthmatic Exacerbation as a Cause of False-Positive Whole-Body Iodine Scan in a Patient With Treated Papillary Thyroid Carcinoma.

A 44-year-old woman was found to have new diffuse lung uptake on a follow-up whole-body I scan 1 year after being treated with surgery and radioactive iodine for papillary thyroid cancer. However, subsequent CT thorax and thyroglobulin levels were both unremarkable. Shortly after, she presented with respiratory symptoms, exhibiting end-expiratory wheezing on auscultation. Metacholine challenge test confirmed asthma. Symptoms improved under inhaled corticosteroids and beta-2 agonists. Resolution of lung uptake was confirmed on a second I imaging 6 months later.

Biopsy-Proven Diffuse Mediastinal Prostate Cancer Metastases Negative on 18F-Fluorocholine, Diagnosed on 68Ga-PSMA and 18F-PSMA PET/CT.

A 72-year-old man with prostate cancer (stage T3b, Gleason score 7) treated by radical prostatectomy was found to have biochemical failure (prostate-specific antigen 8.5 ng/mL) and a suspicious growing nodularity at the left prostate bed on MRI. F-fluorocholine PET/CT failed to demonstrate any site of uptake suggestive of malignancy. A bone scan did exclude bone metastases. Ga-PSMA PET/CT revealed various positive lymph nodes in the supraclavicular, mediastinal, and hilar regions. This was confirmed on F-DCFPyl PET/CT, with the addition of a suspicious right axillary lymph node. Mediastinal biopsy confirmed metastatic prostate cancer.

Erdheim-Chester Disease: The Importance of Information Integration.

BACKGROUND: Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis disorder that utilizes the RAS-RAF-MEK-ERK pathway. It has a highly variable clinical presentation, where virtually any organ can be involved, thus having the potential of posing a great diagnostic challenge. Over half of the reported cases have the BRAF V600E mutation and have shown a remarkable response to vemurafenib. CASE PRESENTATION: We describe herein a patient with a history of stroke-like symptoms and retroperitoneal fibrosis that on initial pathology raised the possibility of IgG4-related disease. However, the patient was refractory to high-dose steroids and progressed further, developing an epicardial soft tissue mass and recurrent neurological symptoms. Integration of the above findings with new information at another hospital about a radiological history of symmetrical lower extremities long bone lesions raised the differential diagnosis of ECD. Molecular analysis of formalin-fixed paraffin-embedded tissue of both of the patient's retroperitoneal biopsies (the second one of which had shown a small focus of foamy histiocytes, CD68+/CD1a-) was positive for BRAF mutation, confirming the diagnosis of ECD. The patient demonstrated a dramatic and sustained metabolic response to vemurafenib on follow-up positron emission tomography scans. CONCLUSION: This case highlights the need for developing a high index of suspicion for presentations of retroperitoneal fibrosis that could represent IgG4-related disease but fail to respond to steroids. When unusual multisystem involvement occurs, one should consider a diagnosis of a rare histiocytosis. Vemurafenib appears to be an effective treatment for even advanced cases of both ECD and Langerhans histiocytosis bearing the BRAF V600E mutation.

Temperament and character personality dimensions in nitrate-tilt-induced vasovagal syncope patients.

OBJECTIVE: Vasovagal syncope (VVS) is a clinical syndrome that is characterized by a transient loss of consciousness and postural tone that are due to a temporary, spontaneously self-terminating global cerebral hypoperfusion. It is known that personality modulates the individual's sensitivity to stressors and that emotional arousal and psychologic uncertainty are conditions that contribute to vasodepressor syncope. Therefore, it is postulated that the personality characteristics of VVS patients could play a role in the pathophysiology of VVS. The aim of our study was to evaluate the temperament and character personality dimensions in patients with VVS as confirmed by nitrate-induced tilt testing. METHODS: From the 450 consecutive patients referred to our Syncope Unit for transient loss of consciousness, we enrolled 162 patients who had positive results from the head up tilt test for VVS and 162 healthy subjects matched for age and sex. All patients underwent a structured clinical interview with a psychologist to exclude the presence of current psychiatric comorbidities and were asked to complete the Cloninger's Temperament and Character Inventory-Revised (TCI-R) questionnaire for psychological assessment. RESULTS: Compared to healthy subjects, both male and female patients with VVS were found to have higher scores of the persistence temperament and self-transcendence character traits. Moreover, male VVS patients had lower scores in "novelty seeking", while female VVS patients scored significantly higher in "reward dependence". CONCLUSION: Our data show that VVS patients significantly differ from matched healthy controls in some temperament and character personality dimensions. Cardiologists should consider referral for psychological assessment when treating patients with refractory VVS.