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Images of DaTscan (ioflupane [123I] SPECT) have been used as an adjunct to clinical diagnosis to facilitate the differential diagnosis of neurodegenerative (ND) Parkinsonian Syndrome (PS) vs. non-dopamine deficiency aetiologies of Parkinsonism. Despite several systematic reviews having summarised the evidence on diagnostic accuracy, the impact of imaging results on clinical utility has not been systematically assessed. Our objective was to examine the available evidence on the clinical utility of DaTscan imaging in changing diagnosis and subsequent management of patients with suspected PS. We performed a systematic review of published studies of clinical utility from 2000 to 2019 without language restrictions. A meta-analysis of change in diagnosis and management rates reported from each study was performed using a random-effects model and logit transformation. Sub-group analysis, meta-regression and sensitivity analysis was performed to explore heterogeneity. Twenty studies met the inclusion criteria. Thirteen of these contributed to the meta-analyses including 950 and 779 patients with a reported change in management and change in diagnosis, respectively. The use of DaTscan imaging resulted in a change in management in 54% (95% CI: 47–61%) of patients. Change in diagnosis occurred in 31% (95% CI: 22–42%) of patients. The two pooled analyses were characterised by high levels of heterogeneity. Our systematic review and meta-analysis show that imaging with DaTscan was associated with a change in management in approximately half the patients tested and the diagnosis was modified in one third. Regardless of time from symptom onset to scan results, these changes were consistent. Further research focusing on specific patient subgroups could provide additional evidence on the impact on clinical outcomes.

Rationale We evaluated K-means clustering to classify amyloid brain PETs as positive or negative. Patients and methods Sixty-six participants (31 men, 35 women; age range, 52-81 years) were recruited through a multicenter observational study: 19 cognitively normal, 25 mild cognitive impairment, and 22 dementia (11 Alzheimer disease, 3 subcortical vascular cognitive impairment, and 8 Parkinson-Lewy Body spectrum disorder). As part of the neurocognitive and imaging evaluation, each participant had an 18F-flutemetamol (Vizamyl, GE Healthcare) brain PET. All studies were processed using Cortex ID software (General Electric Company, Boston, MA) to calculate SUV ratios in 19 regions of interest and clinically interpreted by 2 dual-certified radiologists/nuclear medicine physicians, using MIM software (MIM Software Inc, Cleveland, OH), blinded to the quantitative analysis, with final interpretation based on consensus. K-means clustering was retrospectively used to classify the studies from the quantitative data. Results Based on clinical interpretation, 46 brain PETs were negative and 20 were positive for amyloid deposition. Of 19 cognitively normal participants, 1 (5%) had a positive 18F-flutemetamol brain PET. Of 25 participants with mild cognitive impairment, 9 (36%) had a positive 18F-flutemetamol brain PET. Of 22 participants with dementia, 10 (45%) had a positive 18F-flutemetamol brain PET; 7 of 11 participants with Alzheimer disease (64%), 1 of 3 participants with vascular cognitive impairment (33%), and 2 of 8 participants with Parkinson-Lewy Body spectrum disorder (25%) had a positive 18F-flutemetamol brain PET. Using clinical interpretation as the criterion standard, K-means clustering (K = 2) gave sensitivity of 95%, specificity of 98%, and accuracy of 97%. Conclusions K-means clustering may be a powerful algorithm for classifying amyloid brain PET.

Prophylactic cranial irradiation (PCI) is used to decrease the probability of developing brain metastases in patients with small cell lung cancer and has been linked to deleterious cognitive effects. Although no well-established imaging markers for these effects exist, previous studies have shown that structural and metabolic changes in the brain can be detected with MRI and PET. This study used an image processing technique called texture analysis to explore whether global changes in brain glucose metabolism could be characterized in PET images. Methods:18F-FDG PET images of the brain from patients with small cell lung cancer, obtained before and after the administration of PCI, were processed using texture analysis. Texture features were compared between the pre- and post-PCI images. Results: Multiple texture features demonstrated statistically significant differences before and after PCI when texture analysis was applied to the brain parenchyma as a whole. Regional differences were also seen but were not statistically significant. Conclusion: Global changes in brain glucose metabolism occur after PCI and are detectable using advanced image processing techniques. These changes may reflect radiation-induced damage and thus may provide a novel method for studying radiation-induced cognitive impairment.

After nearly disappearing, invasive lymphangiography not only has resurged, but new approaches have been developed to guide lymphatic interventions. At the same time, noninvasive lymphatic imaging is playing a larger role in the evaluation of lymphatic pathologies. Lymphangioscintigraphy, computed tomography lymphangiography, and magnetic resonance lymphangiography are increasingly being used as alternatives to invasive diagnostic lymphangiography. The purpose of this article is to review current invasive and noninvasive lymphatic imaging techniques.

Background Perivascular epithelioid cell tumors are defined by the World Health Organization as “a collection of rare mesenchymal tumors composed of histologically and immunohistochemically distinctive perivascular epithelioid cells.” Whereas localized perivascular epithelioid cell tumor is typically benign and treated successfully with surgical resection, prognosis for patients with advanced or metastatic perivascular epithelioid cell tumor is unfavorable, and there is no standard curative treatment. Case presentation We report a Caucasian case of metastatic perivascular epithelioid cell tumor previously treated with chemotherapy and surgery with elevated surface expression of programmed cell death ligand 1. Based on this result, treatment via immune checkpoint inhibition with the monoclonal antibody pembrolizumab was pursued. After 21 cycles, the patient sustained a complete response. Therapy was stopped after the 40th cycle, and she was moved to surveillance. She remained disease free 19 months off treatment. Conclusions This case report of a patient with perivascular epithelioid cell tumor treated successfully with programmed cell death protein-1 targeted therapy suggests that programmed cell death ligand-1 levels should be measured in patients with perivascular epithelioid cell tumor and immunotherapy considered for recurrent or metastatic patients. Future phase II/III studies in this disease should focus on sequencing of surgery and immunotherapy with a design of curative intent.

A 74-year-old woman with primary hyperparathyroidism diagnosed from routine laboratory tests described symptoms of fatigue and difficulty with concentration. During surgical consultation, the cervical and thoracic spine MRI scans from the preceding 10-year period, performed for relapsing-remitting multiple sclerosis, were reviewed. In this clinical context, the slowly enlarging left upper paraesophageal lesion, reported as a lateral proximal esophageal (Killian-Jamieson) diverticulum, was reevaluated for a potential parathyroid adenoma. 99mTc-sestamibi SPECT/CT demonstrated focal uptake in the paraesophageal lesion with surgical resection, confirming it to be a large parathyroid adenoma.

Racial and ethnic disparities in the prevalence of neurodegenerative diseases exist. This study examined the agreement between gold standard diagnosis and visual assessment of dopamine transporter (DaT) imaging in Hispanic and non-Hispanic patients being evaluated for Parkinsonian syndromes (PS). Methods: A retrospective review of DaT imaging and demographic data was performed with institutional review board approval. Documented interpretation by visual assessment was used to classify scans as normal or abnormal. The gold standard for the final diagnosis of PS was determined by a neurologist after 2 or more years of clinical follow-up. Data were analyzed with a z-test for uncorrelated samples. Results: In 30 Hispanic patients, DaT imaging was abnormal in 17, normal in 12, and nondiagnostic in 1. Of those with abnormal imaging, PS was confirmed in 16 of 17. Of those with normal imaging, no PS was confirmed in any patient. Sensitivity was 100%, and specificity was 92%. The single patient with nondiagnostic imaging was excluded. Of 77 non-Hispanic patients, visual assessment of DaT imaging was abnormal in 51. Of those with abnormal imaging, PS was confirmed in 48 of 51. Of those with normal imaging, no PS was confirmed in 22 of 26. Sensitivity was 92%, and specificity was 88%. There was no statistically significant difference (z = 0.34) in the rates of agreement between the gold standard and DaT imaging in Hispanic versus non-Hispanic patients. The study sample size afforded a power of 0.60. Conclusion: No significant difference was found in the accuracy of DaT imaging between Hispanic and non-Hispanic patients. Accuracy was high for both groups.

Regadenoson is an adenosine A2A receptor agonist widely used as a pharmacologic stress agent for myocardial perfusion imaging. Approximately 3.4 million regadenoson pharmacologic stress tests were performed annually as of 2011. Caffeine is a competitive antagonist of all adenosine receptor subtypes; thus, caffeine is typically withheld 12-24 h before stress with regadenoson. However, the effects of daily caffeine intake on regadenoson stress are unknown. This study assessed the effects of daily caffeine intake on symptoms and hemodynamic changes during stress testing with regadenoson. Methods: Patients presenting for regadenoson stress myocardial perfusion imaging were asked their amounts of daily caffeine intake. Chart review was used to collect data on demographics, comorbidities, and use of β-blockers. Data collected from the regadenoson stress test included symptoms, administration of aminophylline, heart rate, blood pressure, and arrhythmias. χ2 testing and ANOVA were used to analyze data divided into 3 categories of caffeine intake ( 400 mg daily). χ2 testing was used for nominal data, and unpaired t testing was used for continuous data. Results: In total, 101 patients were enrolled: 53% men and 47% women. Of the 101 patients, 89% reported caffeine intake, with 13% reporting heavy caffeine intake (>400 mg daily). The last intake of caffeine was at least 12 h before the test. During the test, 63% of patients reported symptoms, but the test was completed successfully in all patients. Compared with those who do not use caffeine, intake for caffeine users was associated with less chest pain (P = 0.0013), less aminophylline administration (P = 0.0371), lower resting and peak heart rate (P = 0.0497 and 0.0314, respectively), and lower diastolic blood pressure response (P = 0.0468). No associations were found between caffeine intake and arrhythmia or systolic blood pressure response. Conclusion: The use of regadenoson stress for myocardial perfusion imaging in caffeine consumers is very common, safe, and associated with a lower incidence of certain symptoms than in non-caffeine consumers. Specifically, caffeine intake was associated with less aminophylline use and chest pain.

Research applications of human brain positron emission tomography (PET) imaging have been in place for over 40 years. The unique combination of quantitative PET instrumentation and reconstruction, novel radiotracers, and kinetic modeling has led to the development and application of a huge number of imaging paradigms. These have been applied to the understanding of normal function and pathophysiology, the development of drugs for neuropsychiatric disorders, and the study of drug interactions with the brain. I have had been fortunate to be part of this great endeavor throughout my research career, using brain-dedicated PET scanners, such as the HRRT [item [1] in the Appendix]. Over time, these systems have offered important advantages over whole-body systems. However, due to the limited clinical market for brain PET imaging, scanner manufacturers have focused exclusively on large field-of-view systems for the past two decades [item [2] in the Appendix]. The goal of this perspective is to share a viewpoint on the utility of brain-dedicated PET systems for human research, particularly in the context of novel radiotracers with dynamic studies using kinetic modeling.

Purpose This joint practice guideline or procedure standard was developed collaboratively by the European Association of Nuclear Medicine (EANM) and the Society of Nuclear Medicine and Molecular Imaging (SNMMI). The goal of this guideline is to assist nuclear medicine practitioners in recommending, performing, interpreting, and reporting the results of dopaminergic imaging in parkinsonian syndromes. Methods Currently nuclear medicine investigations can assess both presynaptic and postsynaptic function of dopaminergic synapses. To date both EANM and SNMMI have published procedural guidelines for dopamine transporter imaging with single photon emission computed tomography (SPECT) (in 2009 and 2011, respectively). An EANM guideline for D2 SPECT imaging is also available (2009). Since the publication of these previous guidelines, new lines of evidence have been made available on semiquantification, harmonization, comparison with normal datasets, and longitudinal analyses of dopamine transporter imaging with SPECT. Similarly, details on acquisition protocols and simplified quantification methods are now available for dopamine transporter imaging with PET, including recently developed fluorinated tracers. Finally, [18F]fluorodopa PET is now used in some centers for the differential diagnosis of parkinsonism, although procedural guidelines aiming to define standard procedures for [18F]fluorodopa imaging in this setting are still lacking. Conclusion All these emerging issues are addressed in the present procedural guidelines for dopaminergic imaging in parkinsonian syndromes.

Purpose The aim of this study was to evaluate random forests (RFs) to identify ROIs on F-florbetapir and F-FDG PET associated with Montreal Cognitive Assessment (MoCA) score. Materials and methods Fifty-seven subjects with significant white matter disease presenting with either transient ischemic attack/lacunar stroke or mild cognitive impairment from early Alzheimer disease, enrolled in a multicenter prospective observational trial, had MoCA and F-florbetapir PET; 55 had F-FDG PET. Scans were processed using the MINC toolkit to generate SUV ratios, normalized to cerebellar gray matter (F-florbetapir PET), or pons (F-FDG PET). SUV ratio data and MoCA score were used for supervised training of RFs programmed in MATLAB. Results F-Florbetapir PETs were randomly divided into 40 training and 17 testing scans; 100 RFs of 1000 trees, constructed from a random subset of 16 training scans and 20 ROIs, identified ROIs associated with MoCA score: right posterior cingulate gyrus, right anterior cingulate gyrus, left precuneus, left posterior cingulate gyrus, and right precuneus. Amyloid increased with decreasing MoCA score. F-FDG PETs were randomly divided into 40 training and 15 testing scans; 100 RFs of 1000 trees, each tree constructed from a random subset of 16 training scans and 20 ROIs, identified ROIs associated with MoCA score: left fusiform gyrus, left precuneus, left posterior cingulate gyrus, right precuneus, and left middle orbitofrontal gyrus. F-FDG decreased with decreasing MoCA score. Conclusions Random forests help pinpoint clinically relevant ROIs associated with MoCA score; amyloid increased and F-FDG decreased with decreasing MoCA score, most significantly in the posterior cingulate gyrus.

Molecular and functional imaging aims to assess oncologic therapy response by integrating molecular and functional tumor biology in order to assess therapeutic efficacy and improve patient outcome. Most oncologic processes reflect heterogeneous disease both functionally and morphologically. Further, clonal proliferations of cells may evolve with time becoming resistant to specific therapies. It is important to identify those cancer patients who derive benefit from therapy, such that expensive, toxic, or futile treatment is avoided in those who will not respond. The ultimate goal is to offer the right treatment to the right patient over time. Molecular and functional imaging either using positron emission tomography (PET) or gamma cameras often through hybrid scanners that also include computed tomography (CT) and/or magnetic resonance imaging (MRI) are sensitive techniques with a major role in the precision medicine algorithm of oncology patients. These modalities provide insight prior to, during, and following therapy. Further, they often serve as a biomarker of tumoral heterogeneity helping to direct the selection of appropriate treatment, and detect early response to therapy. Also, molecular and functional imaging is a powerful prognostic biomarker in oncology that can suggest patient outcome based on treatment response.

A 17-year-old girl with World Health Organization grade IV glioblastoma with primitive neuronal components (histone H3 G34-mutant and IDH1 wild type) underwent whole-body FDG PET/CT staging due to vertebral metastases on initial MRI. PET/CT revealed extracranial metastatic disease with spinal leptomeningeal dissemination, osseous metastases, and peritoneal seeding via a ventriculoperitoneal shunt. Glioblastoma is uncommon in pediatric patients and particularly those with primitive neuronal components. Extracranial metastases from glioblastoma are more common in those with primitive neuronal components. This case demonstrates the utility of FDG PET/CT for revealing distant metastases from glioblastoma.

Quantitative assessment of dopamine transporter imaging can aid in diagnosing Parkinson disease (PD) and assessing disease progression in the context of therapeutic trials. Previously, the software program SBRquant was applied to 123I-ioflupane SPECT images acquired on healthy controls and subjects with PD. Earlier work on optimization of the parameters for differentiating between controls and subjects with dopaminergic deficits is extended here for maximizing change measurements associated with disease progression on longitudinally acquired scans. Methods: Serial 123I-ioflupane SPECT imaging for 51 subjects with PD (conducted approximately 1 y apart) were downloaded from the Parkinson Progression Markers Initiative database. The software program SBRquant calculates the striatal binding ratio (SBR) separately for the left and right caudates and putamen regions of interest (ROIs). Parameters were varied to evaluate the number of summed transverse slices and the positioning of the striatal ROIs for determining the signal-to-noise ratio associated with their annual rate of change in SBR. The parameters yielding the largest change in the lowest putamen's SBR from scan 1 to scan 2 were determined. Results: From scan 1 to scan 2 in the 51 subjects, the largest annual change was observed when the putamen ROI was placed 3 pixels away from the caudate and by summing 5 central striatal slices. This resulted in an 11.2% ± 4.3% annual decrease in the lowest putamen SBR for the group. Conclusion: Quantitative assessment of dopamine transporter imaging for assessing progression of PD requires specific, optimal parameters different from those for diagnostic accuracy.

Chemotherapy followed by prophylactic cranial irradiation (PCI) is associated with increased survival in patients with small cell lung cancer but is associated with fatigue and cognitive impairment. This retrospective study evaluated regional differences in 18F-FDG uptake by the brain before and after PCI. The null hypothesis was that direct toxic effects on the brain from PCI and chemotherapy are symmetric; thus, asymmetric deviations may reflect functional changes due to therapy. Methods: Electronic medical records from 2013 to 2016 were reviewed for patients with small cell lung cancer, MRI of brain negative for metastasis, and 18F-FDG PET/CT scans before and after PCI. As the standard of care, patients received first-line chemotherapy or chemoradiation to the thorax followed by PCI. The 18F-FDG PET/CT scans nearest the PCI were selected. Sixteen patients met these initial criteria. Commercially available PET software was used to register and subtract the PET scans before and after PCI to obtain difference maps. Occipital and cerebellar regions were excluded from the final statistical analysis given the known high variability and misregistration. The χ2 test was used to analyze the data. Results: Two patients had 18F-FDG uptake differences only in the occipital and cerebellar regions. The software registration failed on 1 patient's scans. Therefore, 13 patients were included in the final analysis. Nine of 13 patients demonstrated significant unilateral changes in only 1 region of the brain, and 3 of 13 showed significant changes unilaterally in 2 regions. The χ2 test revealed a significant unilateral regional difference on a patient level (χ2 = 6.24, P = 0.025). The most commonly affected brain region was the frontal lobe. Conclusion: Significantly more patients had unilateral than bilateral regional differences (both increases and decreases) in 18F-FDG uptake in the brain before and after PCI. This finding suggests that differences in unilateral distribution are related to functional changes, since direct toxicity alone from PCI and chemotherapy would be symmetric. The frontal region was the most commonly affected, suggesting a potential contributing etiology for cognitive impairment and decreased executive function after therapy.

In this article, we review the literature on PET/CT in the management of dementia, present evidence for best clinical practices, and discuss recent advances in the field.Standard-of-care imaging for dementia includes CT and MRI, primarily for excluding vascular lesions or masses, detecting atrophy, and monitoring disease severity. PET/CT is a powerful functional modality that can differentiate dementia types and influence management. Fluorine-18-FDG PET/CT reveals the spatial pattern of glucose metabolism in the brain. More recently, radiotracers for PET have been developed that bind to amyloid protein, tau protein, and neuroinflammatory markers.

Our primary purpose was to determine whether increased 18F-FDG uptake in the thyroid gland predicts development of thyroiditis with subsequent hypothyroidism in patients undergoing immunotherapy with nivolumab for lung cancer. Secondarily, we determined whether 18F-FDG uptake in the thyroid gland correlates with number of administered cycles of nivolumab. Methods: Retrospective chart review over 2 y found 18 lung cancer patients treated with nivolumab who underwent 18F-FDG PET/CT before and during therapy. SUVmean, SUVmax, and total lesion glycolysis of the thyroid gland were measured. SUVs were also measured for the pituitary gland, liver, and spleen. Patients underwent monthly thyroid testing. PET/CT parameters were analyzed by unpaired t testing for differences between 2 groups (patients who developed hypothyroidism and those who did not). Correlation between development of thyroiditis and number of cycles of nivolumab was also tested. Results: Six of 18 patients developed hypothyroidism. The t test comparing the 2 groups demonstrated significant differences in SUVmean (P = 0.04), SUVmax (P = 0.04), and total lesion glycolysis (P = 0.02) of the thyroid gland. Two of 4 patients who developed thyroiditis and had increased 18F-FDG uptake in the thyroid gland had a normal TSH level at the time of follow-up 18F-FDG PET/CT. Patients who developed thyroiditis with subsequent hypothyroidism stayed longer on therapy (10.6 cycles) than patients without thyroiditis (7.6 cycles), but the trend was not statistically significant. No significant difference in PET/CT parameters was observed for pituitary gland, liver, or spleen. Conclusion:18F-FDG PET/CT can predict the development of thyroiditis with subsequent hypothyroidism before laboratory testing. Further study is required to confirm the positive trend between thyroiditis and duration of therapy.

The brain is the most common site of distant metastasis from lung cancer. Thus, MRI of the brain at initial staging is routinely performed, but if this examination is negative a follow-up examination is often not performed. This study evaluates the incidence of asymptomatic brain metastases in non-small cell lung cancer patients detected on follow-up 18F-FDG PET/CT scans. Methods: In this Institutional Review Board-approved retrospective review, all vertex to thigh 18F-FDG PET/CT scans in patients with all subtypes of lung cancer from August 2014 to August 2016 were reviewed. A total of 1,175 18F-FDG PET/CT examinations in 363 patients were reviewed. Exclusion criteria included brain metastases on initial staging, histologic subtype of small-cell lung cancer, and no follow-up 18F-FDG PET/CT examinations. After our exclusion criteria were applied, a total of 809 follow-up 18F-FDG PET/CT scans in 227 patients were included in the final analysis. The original report of each 18F-FDG PET/CT study was reviewed for the finding of brain metastasis. The finding of a new brain metastasis prompted a brain MRI, which was reviewed to determine the accuracy of the 18F-FDG PET/CT. Results: Five of 227 patients with 809 follow-up 18F-FDG PET/CT scans reviewed were found to have incidental brain metastases. The mean age of the patients with incidental brain metastasis was 68 y (range, 60-77 y). The mean time from initial diagnosis to time of detection of incidental brain metastasis was 36 mo (range, 15-66 mo). When MRI was used as the gold standard, our false-positive rate was zero. Conclusion: By including the entire head during follow-up 18F-FDG PET/CT scans of patients with non-small cell lung cancer, brain metastases can be detected earlier while still asymptomatic. But, given the additional scan time, radiation, and low incidence of new brain metastases in asymptomatic patients, the cost-to-benefit ratio should be weighed by each institution.

We present a case of an immunocompetent 27-year-old African American man who was initially diagnosed with diffuse pulmonary coccidioidomycosis and started on oral fluconazole. While his symptoms improved, he began to develop tender cutaneous lesions. Biopsies of the cutaneous lesions grew Coccidioides immitis. Subsequent 18F-FDG PET/CT revealed extensive multisystem involvement including the skin/subcutaneous fat, lungs, spleen, lymph nodes, and skeleton. This case demonstrates the utility of obtaining an 18F-FDG PET/CT to assess the disease extent and activity in patients with disseminated coccidioidomycosis who initially present with symptoms involving only the lungs.

While various modalities exist for the diagnosis of pulmonary embolism (PE), CT pulmonary angiography (CTPA) is the most widely used and can establish the diagnosis quickly and reliably. We report a patient who presented with syncope who developed pulseless electrical activity (PEA) arrest in the emergency department. Given the presence of acute renal injury, CTA was felt to be contraindicated. A ventilation-perfusion lung (VQ) scan demonstrated low probability for PE; however, echocardiography revealed evidence for right heart strain. Subsequent cardiac magnetic resonance imaging (CMR) unexpectedly revealed a saddle PE. This case highlights the potential role for MR for the diagnosis of PE when high clinical suspicion is discordant with results of conventional imaging.

Osteosarcoma (OS) is a malignant bone tumor which is found primarily in adolescents, with the distal femur as the most common location. OS with a jaw primary is present in only about 10% of cases and the risk of recurrence is considered to be decreased in the jaw versus other primary locations. We present a unique case of a patient with localized OS of the jaw with an isolated recurrence in her bone marrow almost 5 years after completion of initial treatment.

An 85-year-old man with stage IIIA Merkel cell carcinoma of the left arm was initially treated with local excision and axillary node dissection followed by radiation therapy. Eight months after surgery, whole-body FDG PET/CT demonstrated intensely hypermetabolic hepatic metastases and abdominal lymphadenopathy. Given his age and comorbidities, he was considered a poor candidate for chemotherapy, and therefore the novel programmed cell death ligand 1 inhibitor avelumab was initiated. FDG PET/CT after 4 cycles showed complete resolution of hepatic and nodal metastases. Whole-body FDG PET/CT can be used for monitoring response of multisystem metastases from Merkel cell carcinoma to active immunotherapy.

A 61-year-old woman with lung adenocarcinoma failed first-line treatment and was placed on immunotherapy with nivolumab. FDG-PET/CT before immunotherapy showed metastases to thoracic nodes, liver, adrenal gland, and skeleton. Seven weeks after starting nivolumab, FDG-PET/CT showed mild residual activity in thoracic nodes and otherwise complete response. After 15 weeks, enlarged and FDG-avid axillary lymphadenopathy and worsening supraclavicular lymphadenopathy developed. After 20 weeks, FDG-PET/CT demonstrated marked improvement of axillary and supraclavicular lymphadenopathy. This case demonstrates that later progression of disease can still respond to continuing immunotherapy, hypothetically because of dynamic adaptations in the tug-of-war between the immunotherapy-augmented immune system and tumor.

PET using FDG is a critical tool for evaluation of dementias, with characteristic patterns of hypometabolism suggesting specific diagnoses. Hypometabolism in the occipital region is recognized as an important finding associated with dementia with Lewy bodies and posterior cortical atrophy. We describe here the novel "occipital tunnel" sign, which results from relative sparing of FDG uptake in the medial occipital (primary visual) cortex compared with more severe loss in the surrounding lateral occipital (visual association) cortex. This sign is useful for recognizing the occipital findings of dementia with Lewy bodies and posterior cortical atrophy, especially when viewing sagittal projections.

90Y radioembolization is a safe and efficacious treatment option for many patients with unresectable hepatocellular carcinoma. Potential candidates for radioembolization, based on clinical criteria, undergo 99mTc-labeled macroaggregated albumin imaging to determine the extent of hepatopulmonary shunting. Dose selection is based on results from shunt imaging and can exclude patients from radioembolization therapy. We present a case of miscalculated lung shunt fraction and the circumstances that led to the critical error.

Machine learning (ML) is increasingly used in medical imaging. This paper provides pilot data of decision trees and random forests (RFs) to predict if a 18F-florbetapir brain positron emission tomography (PET) is positive or negative for amyloid deposition based on quantitative data analysis. The dataset included 55 18F-florbetapir brain PETs in participants with severe white matter disease and mild cognitive impairment (MCI), early Alzheimer's disease (AD) or transient ischemic events. The Montreal Cognitive Assessment (MoCA) score was known for each participant. All PET images were processed using the MINC toolkit to extract standardized uptake value ratios (SUVRs) for 59 regions of interest (features). Each PET was clinically read by 2 dual certified radiology/nuclear medicine physicians with final interpretation based on consensus. An initial study of RFs using conventional binary decision trees and PET quantitation suggests this is a powerful algorithm for PET classification as positive or negative for amyloid deposition. Preliminary data did not show improved results when a ternary RF approach was used. Finally, a soft-decision approach may be helpful to predict the $\mathbf{MoCA}$ score.

We optimized acido-chemical exchange saturation transfer (acidoCEST) magnetic resonance imaging (MRI), a method that measures extracellular pH (pHe), and translated this method to the radiology clinic to evaluate tumor acidosis. A CEST-FISP MRI protocol was used to image a flank SKOV3 tumor model. Bloch fitting modified to include the direct estimation of pH was developed to generate parametric maps of tumor pHe in the SKOV3 tumor model, a patient with high-grade invasive ductal carcinoma, and a patient with metastatic ovarian cancer. The acidoCEST MRI results of the patient with metastatic ovarian cancer were compared with DCE MRI and histopathology. The pHe maps of a flank model showed pHe measurements between 6.4 and 7.4, which matched with the expected tumor pHe range from past acidoCEST MRI studies in flank tumors. In the patient with metastatic ovarian cancer, the average pHe value of three adjacent tumors was 6.58, and the most reliable pHe measurements were obtained from the right posterior tumor, which favorably compared with DCE MRI and histopathological results. The average pHe of the kidney showed an average pHe of 6.73 units. The patient with high-grade invasive ductal carcinoma failed to accumulate sufficient agent to generate pHe measurements. Optimized acidoCEST MRI generated pHe measurements in a flank tumor model and could be translated to the clinic to assess a patient with metastatic ovarian cancer.

Purpose Dopamine transporter single-photon emission computed tomography imaging utilizing iodine-123 ioflupane is accurate for differentiation of Parkinson disease from essential tremor. This study evaluates how reimbursement for I-123 ioflupane imaging changed between 2011 (year of FDA approval) and 2014 (year after loss of pass-through status for hospital-based outpatient imaging from CMS). Methods I-123 ioflupane reimbursement data for our institution's hospital-based imaging were compared between two periods: (1) July 2011 to October 2012, and (2) 2014. For each time period separately and in combination, averages and ranges of reimbursement for private insurance and CMS were analyzed and compared. A model to ensure recouping of radiopharmaceutical costs was developed. Results Review yielded 247 studies from July 2011 to October 2012 and 94 studies from 2014. Average reimbursement per study fell from $2,469 (US dollars) in 2011 to 2012 to $1,657 in 2014. CMS reduced average reimbursement by $1,148 in 2014 because of loss of radiopharmaceutical pass-through status. Average reimbursements from CMS versus private payors markedly differed in 2011 to 2012 at $2,266 versus $2,861, respectively, and in 2014 at $1,118 versus $3,470, respectively. Between 2011 to 2012 and 2014, the CMS percentage increased from 54% to 78%. Assuming that I-123 ioflupane cost $2,000, our model based on 2014 data predicts a practice with greater than 60% CMS patients would no longer recover radiopharmaceutical costs. Conclusions Reimbursement levels, payor mix, scanner location, and radiopharmaceutical costs are all critical, variable factors for modeling the financial viability of I-123 ioflupane imaging and, by extrapolation, future radiopharmaceuticals.

Establishing a diagnosis of Alzheimer dementia can be challenging, particularly early in the course of the disease. However, with disease-modifying therapies on the horizon, it is becoming increasingly important to achieve the correct diagnosis as soon as possible. In challenging presentations of dementia, such as patients with clinically atypical features or early-age onset of mild cognitive impairment, amyloid PET is a valuable tool in determining the diagnosis of Alzheimer dementia. Furthermore, preliminary data show that amyloid PET findings alter clinical management in patients who meet the appropriate use criteria. There are currently three U.S. Food and Drug Administration (FDA)-approved fluorine 18 (18F)-labeled radiopharmaceuticals that allow in vivo detection of cerebral amyloid deposition, which is a hallmark pathologic feature of Alzheimer dementia. Knowledge of the common imaging features among these three 18F-labeled radiopharmaceuticals in the normal and abnormal brain will enable the radiologist to more accurately interpret amyloid PET studies. As in other subspecialties of radiology, imaging signs in amyloid PET are helpful to distinguish if a region is normal or abnormal. This article reviews appropriate use criteria for amyloid PET, introduces the properties of the radiopharmaceuticals, explains the algorithmic approach to interpretation with examples of normal and abnormal amyloid PET scans with MRI correlation, and provides an atlas of regional amyloid PET signs and common artifacts. ©RSNA, 2018.

Infection with Coccidioides immitis , a soil-dwelling fungus endemic to the American Southwest, may have protean manifestations in immunocompromised patients who reside in1 2 or who have travelled to3 that region. We report a patient whose abnormal PET/CT scan raised concern for recurrent lymphoma but instead was due to disseminated coccidioidomycosis. A 62-year-old woman was diagnosed with ileocaecal marginal zone lymphoma (MZL) after presenting with iron-deficiency anaemia and faecal occult blood. Ten years earlier, she underwent allogeneic haematopoietic cell transplantation for acute myeloid leukaemia (AML). She had recurrent cutaneous chronic graft-versus-host-disease (CGVHD); 50 months before the diagnosis of MZL, she completed a 9-month course of …

Dementia is an important cause of morbidity and mortality worldwide and encompasses a very heterogenous group of disease processes. Positron emission tomography (PET) of the brain using fluorodeoxyglucose (FDG) is a useful modality for differentiating types of dementia. Because FDG does not bind to pathologic proteins, FDG-PET requires that the reader recognize characteristic patterns of glucose hypometabolism to identify pathology. These patterns have been documented in the literature for both primary neurodegenerative disorders and secondary causes of dementia. This article presents an algorithm for organizing these findings and systematically applying them to interpret FDG-PET brain imaging for dementia.

A 56-y-old man underwent total thyroidectomy and bilateral central and right lateral neck dissection for papillary thyroid carcinoma with lymph nodes metastases. Before radioiodine ablation, a 123I scan established the diagnosis of primary nasolacrimal duct obstruction (dacryostenosis).

A 65-year-old woman with metastatic lung cancer was referred for CT-guided cryoablation of a right adrenal metastasis. For cryoablation, probes were placed into the adrenal region. FDG PET/CT 3 months later showed new activity in hepatic segment 6 initially suspected to be metastasis. Proximity of the hepatic lesion to the adrenal metastasis was a strange coincidence and prompted review of imaging from the cryoablation. CT showed the probe entered the liver, and postablation image demonstrated injury to the liver adjacent to the adrenal metastasis. Careful review of treatment history and imaging from ablation procedures are important to avoid this pitfall.

Relapse of acute lymphoblastic leukemia (ALL) in the breast is uncommon and often precedes systemic relapse, resulting in poor survival. We report the development of breast involvement of ALL in a 20-year-old woman 32 months after a related allogeneic peripheral blood hematopoietic cell transplantation (PBHCT) in first remission. This extramedullary relapse occurred in the continuous presence of complete donor chimerism. After systemic re-induction chemotherapy and a second PBHCT using donor cells that had been cryopreserved at first transplant, our patient has remained in second complete remission for more than 44 months.

OBJECTIVE Nuclear imaging can confirm pleuroperitoneal shunt as the cause of pleural effusion. No society guidelines exist for scintigraphic pleuroperitoneal shunt detection. Our institutional protocol was evaluated to determine optimal imaging time points for shunt detection. METHODS Pleuroperitoneal shunt studies over 4 years were blindly reviewed by 2 nuclear radiologists. Data from blinded review included presence or absence of pleuroperitoneal shunt, laterality of shunt and time points for shunt detection. RESULTS Chart review yielded 30 studies. Three cases were excluded because of improper injection. Imaging was positive for pleuroperitoneal shunt in 81% (22/27) of cases. In positive cases, activity was identified in the right hemithorax in 82% (18/22), left hemithorax in 9% (2/22), and bilaterally in 9% (2/22). One-hour imaging demonstrated 91% (20/22) of positive cases. The remaining 2 positive cases were negative at 1 hour but positive after 4 hours. No study was negative at 1 and 4 hours and positive at 24 hours. All negative cases (5/27) were confirmed on 24-hour imaging. CONCLUSIONS The majority of positive pleuroperitoneal shunt examinations will demonstrate activity in the right hemithorax on 1-hour imaging. Although no case was negative at 1 and 4 hours and positive at 24 hours, imaging at 24 hours may still be necessary to confirm absence of shunt. Therefore, optimal imaging time points consist of early 1-hour and delayed 24-hour images if the 1-hour time point was negative. The 4-hour time point may be considered optional, thereby potentially optimizing patient safety and resource utilization.

F-NaF PET/CT is an evolving technique that provides high sensitivity for detection of osseous metastases. In addition to detecting pathological osseous lesions, F uptake is occasionally detected in extraosseous lesions. However, reporting of extraosseous uptake in the literature is limited, and the increasing use of F-NaF PET/CT dictates that interpreting physicians learn to recognize extraosseous findings. An atlas of extraosseous findings detected by F-NaF PET/CT is presented, which includes cases under 2 broad categories: nonneoplastic and neoplastic.

A 41-year-old man with gastric adenocarcinoma presented with hepatic metastases. The metastases were refractory to systemic chemotherapy, so radioembolization with Y microspheres was performed. Because of stasis or saturation of the tumor with embolic particles, 79% of the microspheres were injected. At follow-up, the patient complained of "red bumps" that had developed on his right foot/ankle the day after the radioembolization. Because a portion of the dose was still in the catheter when withdrawn from the right femoral artery, the interventional radiologist used a Geiger counter to confirm radioactivity in the cutaneous lesions and thus the distal embolization of the microspheres.

Visual interpretation of 123I-ioflupane SPECT images has high diagnostic accuracy for differentiating parkinsonian syndromes (PS), from essential tremor and probable dementia with Lewy bodies (DLB) from Alzheimer disease. In this study, we investigated the impact on accuracy and reader confidence offered by the addition of image quantification in comparison with visual interpretation alone. Methods: We collected 304 123I-ioflupane images from 3 trials that included subjects with a clinical diagnosis of PS, non-PS (mainly essential tremor), probable DLB, and non-DLB (mainly Alzheimer disease). Images were reconstructed with standardized parameters before striatal binding ratios were quantified against a normal database. Images were assessed by 5 nuclear medicine physicians who had limited prior experience with 123I-ioflupane interpretation. In 2 readings at least 1 mo apart, readers performed either a visual interpretation alone or a combined reading (i.e., visual plus quantitative data were available). Readers were asked to rate their confidence of image interpretation and judge scans as easy or difficult to read. Diagnostic accuracy was assessed by comparing image results with the standard of truth (i.e., diagnosis at follow-up) by measuring the positive percentage of agreement (equivalent to sensitivity) and the negative percentage of agreement (equivalent to specificity). The hypothesis that the results of the combined reading were not inferior to the results of the visual reading analysis was tested. Results: A comparison of the combined reading and the visual reading revealed a small, insignificant increase in the mean negative percentage of agreement (89.9% vs. 87.9%) and equivalent positive percentages of agreement (80.2% vs. 80.1%). Readers who initially performed a combined analysis had significantly greater accuracy (85.8% vs. 79.2%; P = 0.018), and their accuracy was close to that of the expert readers in the original studies (range, 83.3%-87.2%). Mean reader confidence in the interpretation of images showed a significant improvement when combined analysis was used (P < 0.0001). Conclusion: The addition of quantification allowed readers with limited experience in the interpretation of 123I-ioflupane SPECT scans to have diagnostic accuracy equivalent to that of the experienced readers in the initial studies. Also, the results of the combined reading were not inferior to the results of the visual reading analysis and offered an increase in reader confidence.

An automated objective striatal analysis (OSA) software program was applied to dopamine transporter 123I-ioflupane images acquired on subjects with varying severities of parkinsonism. The striatal binding ratios (SBR) of the left and right putamina (relative to the occipital lobe) were computed, and the laterality of that measure was compared with clinical symptoms and visual reads. The objective over-read of OSA was evaluated as an aid in confirming the laterality of disease onset. Methods: One hundred one 123I-ioflupane scans were acquired on clinically referred subjects. SPECT images were analyzed using the OSA software, which locates the slices containing the striatal and background (occipital) structures, positions regions over the left and right caudate nuclei and putamina, and calculates the background-subtracted SBR. Seven images were uninterpretable because of patient motion or lack of visualization of the striatum. The remaining 94 scans were analyzed with OSA. Differences between left and right putaminal SBR ranged from 0% to 36.6%, with a mean of 11.4%. When the difference between the SBR of the left and right putamina was greater than 6%, the lower side was taken as the side of onset. Left-to-right differences less than 6% were considered to be nonlateralizing (symmetric). The 94 scans were reviewed independently by 3 masked expert readers. By majority consensus, abnormal findings were seen on 67 of the 94 scans, of which 46 had available clinical findings. Results: Clinically, 34 subjects presented with lateralized tremors and 12 with symmetric or no tremors. Of the 34 cases of clinically lateralized tremors, 26 (76%) were concordant with the OSA findings, 5 were disparate with OSA (15%), and in 3 the OSA results were symmetric (9%). For the same 34 patients, the visual reads were concurrent with clinical tremor findings in 24 cases (71%), 1 was disparate (3%), and 9 visual reads were symmetric (26%). Of the 9 scans deemed symmetric by readers, 4 were correctly lateralized by OSA, and of the 3 symmetric OSA results, 2 were correctly lateralized visually. Conclusion: The OSA program may be a helpful aid in the interpretation of 123I-ioflupane SPECT images for determining laterality representing the asymmetric loss of dopamine transporters in the striata. OSA offers an objective, reproducible over-read evaluation for the laterality of onset in Parkinson disease.

61-year-old woman with stage IIIa (T3a N1a M0) left lower leg melanoma with lesions suggestive of in-transit metastases 8 months following wide local excision and femoral nodal dissection. FDG-PET/CT demonstrated 5 FDG-avid in-transit nodal metastases in the distal left leg, confirmed on biopsy. Talimogene laherparepvec (T-VEC) oncolytic immunotherapy consisting of intralesional injections of modified herpes simplex virus-expressing granulocyte-macrophage colony-stimulating factor was completed over 6 months. Subsequent FDG-PET/CT demonstrated reduced or resolved FDG activity in the treated in-transit metastases and a new FDG-avid left thigh in-transit metastasis. FDG-PET/CT can monitor response to T-VEC and potentially other novel viral immunotherapies.

A 21-y-old man who presented with polyuria and polydipsia was discovered to have diabetes insipidus due to eosinophilic granuloma of the hypothalamus. 18F-FDG PET/CT, which was performed as a metastatic work-up, revealed an intensely 18F-FDG-avid hypothalamic mass and no other sites of disease.

Ascites can cause pleural effusions when the peritoneal fluid crosses the diaphragm through a pleuroperitoneal shunt in the setting of hepatic cirrhosis (hepatic hydrothorax) or malignant ascites. Scintigraphic imaging for pleuroperitoneal shunt requires intraperitoneal injection of Tc-SC or Tc-macroaggregated albumin followed by planar imaging of the chest and abdomen. Pleuroperitoneal shunt is confirmed by identifying radiotracer crossing the diaphragm from the peritoneal to pleural space. An atlas of pleuroperitoneal shunt imaging pitfalls is presented to facilitate optimal performance and interpretation of nuclear pleuroperitoneal shunt examinations. Examples include cases of nondiagnostic radiotracer injections, processing errors, and nontarget uptake.

A 38-year-old woman with metastatic breast carcinoma reported seeing "halos and flashes" in her left eye. Funduscopic exam revealed an elevated mass in the choroid of the left globe consistent with metastasis. Subsequent 18F-FDG PET/CT revealed focal uptake in the nasal aspect of the left choroid of the eye corresponding to the mass seen on the funduscopic exam. Through correlation with the PET/CT, the lesion was retrospectively identified on the MRI. 18F-FDG PET/CT post-radiotherapy showed complete response and thus supports that this imaging modality can be used for diagnosis and monitoring response. History of breast cancer and visual symptoms should trigger the nuclear medicine physician to take extra care in reading the initial slices of the PET/CT scan through the orbits in order to make this challenging imaging diagnosis.

272 Background: Prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancers, making it an ideal imaging and therapeutic target of interest. The utility of the PSMA-targeted imaging agent 99mTc-EC0652 is being evaluated, along with biomarker analysis of circulating tumor cells (CTCs), in pts with mCRPC in a PSMA-targeted chemotherapeutic study. We now report the PSMA heterogeneity via CTC vs. imaging in the pt population treated to date. Methods: Patients were enrolled in 1 of 2 cohorts: mCRPC taxane naïve or taxane exposed. A total of 48 pts evaluated at the time of the data cut had baseline CT & bone scans performed in addition to a 99mTc-EC0652 SPECT/CT as a measure of imaging-based PSMA expression. 40 of 48 pts provided pre-treatment blood samples evaluable for CTC biomarker analysis, which included PSMA expression & were given percent homologous recombination deficiency (%HRD) scores. Four of the best and four of the worst responders were evaluated in more detail for imaging and CTC-based biomarker analysis as it related to clinical outcome. Results: 35 of 40 pts (88%) had detectable CTCs in their samples. 15 of the 35 (43%) pts had PSMA-positive CTCs. The 4 “non-responders” were on study for an average of 41 days and the 4 “responders” for an average of 256 days. Each group contained 2 taxane exposed & 2 taxane naïve patients. Of the 335 bone lesions analyzed by MDP, CT, 99mTc-EC0652, 333 (99.4%) were characterized as PSMApos based on their 99mTc-EC0652 SPECT/CT scan. Of the 26 soft tissue lesions analyzed by CT, all were characterized as PSMApos based on their 99mTc-EC0652 SPECT/CT scan. Seven (26.9%) of those lesions were CT positive (observed on CT scan). Each group had 2 pts that were CTC-based PSMApos & 2 that were PSMAneg. Their percent homologous recombination deficiency (%HRD) scores were of 0.60 [0.333, 1.0] for “non-responders” & 0.01 [0.0, 0.039] for “responders”. Conclusions: PSMA-based imaging showed a high percentage of positive lesions whereas CTC-based PMSA positivity is lower by comparison (43%). The discordance between the imaging results & CTC-based biomarkers, & the relative therapeutic predictive value, requires additional exploration. Clinical trial information: NCT02202447.

A patient with systemic mastocytosis underwent a FDG-PET/CT scan. CT demonstrated loss of corticomedullary differentiation in the axial skeleton and thickening of cortical bone in the appendicular skeleton consistent with myelofibrosis and osteosclerosis. Remarkably, the bones of the lower