Deep generative modeling of the human proteome reveals over a hundred novel genes involved in rare genetic disorders.

Identifying causal mutations accelerates genetic disease diagnosis, and therapeutic development. Missense variants present a bottleneck in genetic diagnoses as their effects are less straightforward than truncations or nonsense mutations. While computational prediction methods are increasingly successful at prediction for variants in known disease genes, they do not generalize well to other genes as the scores are not calibrated across the proteome1-6. To address this, we developed a deep generative model, popEVE, that combines evolutionary information with population sequence data7 and achieves state-of-the-art performance at ranking variants by severity to distinguish patients with severe developmental disorders8 from potentially healthy individuals9. popEVE identifies 442 genes in patients this developmental disorder cohort, including evidence of 123 novel genetic disorders, many without the need for gene-level enrichment and without overestimating the prevalence of pathogenic variants in the population. A majority of these variants are close to interacting partners in 3D complexes. Preliminary analyses on child exomes indicate that popEVE can identify candidate variants without the need for inheritance labels. By placing variants on a unified scale, our model offers a comprehensive perspective on the distribution of fitness effects across the entire proteome and the broader human population. popEVE provides compelling evidence for genetic diagnoses even in exceptionally rare single-patient disorders where conventional techniques relying on repeated observations may not be applicable.

Deep generative modeling of the human proteome reveals over a hundred novel genes involved in rare genetic disorders.

Identifying causal mutations accelerates genetic disease diagnosis, and therapeutic development. Missense variants present a bottleneck in genetic diagnoses as their effects are less straightforward than truncations or nonsense mutations. While computational prediction methods are increasingly successful at prediction for variants in known disease genes, they do not generalize well to other genes as the scores are not calibrated across the proteome. To address this, we developed a deep generative model, popEVE, that combines evolutionary information with population sequence data and achieves state-of-the-art performance at ranking variants by severity to distinguish patients with severe developmental disorders from potentially healthy individuals. popEVE identifies 442 genes in a cohort of developmental disorder cases, including evidence of 119 novel genetic disorders without the need for gene-level enrichment and without overestimating the prevalence of pathogenic variants in the population. By placing variants on a unified scale, our model offers a comprehensive perspective on the distribution of fitness effects across the entire proteome and the broader human population. popEVE provides compelling evidence for genetic diagnoses even in exceptionally rare single-patient disorders where conventional techniques relying on repeated observations may not be applicable. Interactive web viewer and downloads available at pop.evemodel.org.

ProteinGym: Large-Scale Benchmarks for Protein Design and Fitness Prediction.

Predicting the effects of mutations in proteins is critical to many applications, from understanding genetic disease to designing novel proteins that can address our most pressing challenges in climate, agriculture and healthcare. Despite a surge in machine learning-based protein models to tackle these questions, an assessment of their respective benefits is challenging due to the use of distinct, often contrived, experimental datasets, and the variable performance of models across different protein families. Addressing these challenges requires scale. To that end we introduce ProteinGym, a large-scale and holistic set of benchmarks specifically designed for protein fitness prediction and design. It encompasses both a broad collection of over 250 standardized deep mutational scanning assays, spanning millions of mutated sequences, as well as curated clinical datasets providing high-quality expert annotations about mutation effects. We devise a robust evaluation framework that combines metrics for both fitness prediction and design, factors in known limitations of the underlying experimental methods, and covers both zero-shot and supervised settings. We report the performance of a diverse set of over 70 high-performing models from various subfields (eg., alignment-based, inverse folding) into a unified benchmark suite. We open source the corresponding codebase, datasets, MSAs, structures, model predictions and develop a user-friendly website that facilitates data access and analysis.

A conformal TOF-DOI Prism-PET prototype scanner for high-resolution quantitative neuroimaging.

BACKGROUND: Positron emission tomography (PET) has had a transformative impact on oncological and neurological applications. However, still much of PET's potential remains untapped with limitations primarily driven by low spatial resolution, which severely hampers accurate quantitative PET imaging via the partial volume effect (PVE). PURPOSE: We present experimental results of a practical and cost-effective ultra-high resolution brain-dedicated PET scanner, using our depth-encoding Prism-PET detectors arranged along a compact and conformal gantry, showing substantial reduction in PVE and accurate radiotracer uptake quantification in small regions. METHODS: The decagon-shaped prototype scanner has a long diameter of 38.5 cm, a short diameter of 29.1 cm, and an axial field-of-view (FOV) of 25.5 mm with a single ring of 40 Prism-PET detector modules. Each module comprises a 16 × 16 array of 1.5 × 1.5 × 20-mm3 lutetium yttrium oxyorthosillicate (LYSO) scintillator crystals coupled 4-to-1 to an 8 × 8 array of silicon photomultiplier (SiPM) pixels on one end and to a prismatoid light guide array on the opposite end. The scanner's performance was evaluated by measuring depth-of-interaction (DOI) resolution, energy resolution, timing resolution, spatial resolution, sensitivity, and image quality of ultra-micro Derenzo and three-dimensional (3D) Hoffman brain phantoms. RESULTS: The full width at half maximum (FWHM) DOI, energy, and timing resolutions of the scanner are 2.85 mm, 12.6%, and 271 ps, respectively. Not considering artifacts due to mechanical misalignment of detector blocks, the intrinsic spatial resolution is 0.89-mm FWHM. Point source images reconstructed with 3D filtered back-projection (FBP) show an average spatial resolution of 1.53-mm FWHM across the entire FOV. The peak absolute sensitivity is 1.2% for an energy window of 400-650 keV. The ultra-micro Derenzo phantom study demonstrates the highest reported spatial resolution performance for a human brain PET scanner with perfect reconstruction of 1.00-mm diameter hot-rods. Reconstructed images of customized Hoffman brain phantoms prove that Prism-PET enables accurate radiotracer uptake quantification in small brain regions (2-3 mm). CONCLUSIONS: Prism-PET will substantially strengthen the utility of quantitative PET in neurology for early diagnosis of neurodegenerative diseases, and in neuro-oncology for improved management of both primary and metastatic brain tumors.

Extensive Nonsegmental Pulmonary Perfusion Defects on SPECT/CT as an Early Sign of COVID-19 Infection.

We describe a hospitalized patient with confirmed coronavirus disease 2019 in whom the initial chest computed tomography (CT) was negative, while subsequent perfusion single-photon emission computed tomography/computed tomography imaging revealed extensive nonsegmental perfusion defects in addition to newly developing parenchymal densities. Possible reasons for these findings and their relationship to the multisystem severe acute respiratory syndrome coronavirus 2 infection are discussed in this article.

"Low Dose MR" Dixon Technique for Imaging FDG PET-MR Lymphoma.

Introduction Hybrid PET-MR is a relatively new imaging modality with its major strength being the MR component offering superior soft tissue contrast. While PET/MRI offers the inherent advantage of reduced radiation dose, it has been shown to result in a markedly prolonged examination time becoming a challenge in children and sick patients. "Low dose MRI" is a term used in the nuclear medicine community to describe fast acquired PET-MR scan protocols that rely heavily on PET images for diagnosis. In this study, we sought to determine if the Dixon sequences obtained for attenuation correction could be used as a diagnostic sequence for interpreting PET-MRI lymphoma cases, potentially reducing scan time. Materials and Methods We retrospectively identified 40 patients who underwent 88 FDG PET-MR body imaging studies for staging or restaging lymphoma. A radiologist and nuclear medicine physician initially reviewed top of the head to mid thigh PET images, attenuation correction coronal Dixon MRI sequences, and PET-MR fusion with Dixon sequence. The same physicians reviewed the PET images, multi-sequence MR including the attenuation correction Dixon, and multi-sequence PET-MR fusion images The lesions were further characterized based on their imaging characteristics, size, SUVmax, and malignant potency. A consensus read followed. Results All patients were adults with an average study age of 43.8 years. Our study consisted of 40 females and 48 males out of which 7 were for staging and 81 were for re-staging. All patients had systemic lymphoma. Thirty-seven of the studies had active lymph nodes on Dixon PET-MR that agreed with multi-sequence PET-MR which identified 33 positive cases (89.1%) having an average SUV 10.2 ± 7.74 SD. Four Dixon PET-MR cases did not detect lesions, with an average SUV 2.3 ± 0.55 SD, which was read as minimal residual activity. Multi-sequence MR identified 11 patients with enlarged lymph nodes without FDG uptake, which were not seen on Dixon MR. All 5 studies with bones lesions were detected by Dixon PET-MR as well as 2 soft tissue organ lesions. Multi-sequence MR identified 1 patient with non-active, healed bone lesion. Fifty-five of these studies were true negatives. Compared to multi-sequence PET-MR, Dixon PET-MR demonstrated 89.2% sensitivity, 100% specificity with no false positive studies. Conclusion The present study investigated the diagnostic potential of a fast protocol for integrated PET/MRI used for dedicated tumor staging of patients with lymphoma. In this retrospective study, Dixon PET-MR was shown to be sensitive and specific compared to multi-sequence PET-MR in the detection of lymphoma. The low number of these cases not detected had minimally active lymph nodes that resolved on subsequent imaging and probably were not clinically important.

Modulation of Secondary Cancer Risks from Radiation Exposure by Sex, Age and Gonadal Hormone Status: Progress, Opportunities and Challenges.

Available data on cancer secondary to ionizing radiation consistently show an excess (2-fold amount) of radiation-attributable solid tumors in women relative to men. This excess risk varies by organ and age, with the largest sex differences (6- to more than 10-fold) found in female thyroid and breasts exposed between birth until menopause (~50 years old) relative to age-matched males. Studies in humans and animals also show large changes in cell proliferation rates, radiotracer accumulation and target density in female reproductive organs, breast, thyroid and brain in conjunction with physiological changes in gonadal hormones during the menstrual cycle, puberty, lactation and menopause. These sex differences and hormonal effects present challenges as well as opportunities to personalize radiation-based treatment and diagnostic paradigms so as to optimize the risk/benefit ratios in radiation-based cancer therapy and diagnosis. Specifically, Targeted Radionuclide Therapy (TRT) is a fast-expanding cancer treatment modality utilizing radiopharmaceuticals with high avidity to specific molecular tumor markers, many of which are influenced by sex and gonadal hormone status. However, past and present dosimetry studies of TRT agents do not stratify results by sex and hormonal environment. We conclude that cancer management using ionizing radiation should be personalized and informed by the patient sex, age and hormonal status.

High-resolution and high-sensitivity PET for quantitative molecular imaging of the monoaminergic nuclei: A GATE simulation study.

PURPOSE: Quantitative in vivo molecular imaging of fine brain structures requires high-spatial resolution and high-sensitivity. Positron emission tomography (PET) is an attractive candidate to introduce molecular imaging into standard clinical care due to its highly targeted and versatile imaging capabilities based on the radiotracer being used. However, PET suffers from relatively poor spatial resolution compared to other clinical imaging modalities, which limits its ability to accurately quantify radiotracer uptake in brain regions and nuclei smaller than 3 mm in diameter. Here we introduce a new practical and cost-effective high-resolution and high-sensitivity brain-dedicated PET scanner, using our depth-encoding Prism-PET detector modules arranged in a conformal decagon geometry, to substantially reduce the partial volume effect and enable accurate radiotracer uptake quantification in small subcortical nuclei. METHODS: Two Prism-PET brain scanner setups were proposed based on our 4-to-1 and 9-to-1 coupling of scintillators to readout pixels using 1.5 × 1.5 × 20 $1.5 \times 1.5 \times 20$  mm3 and 0.987 × 0.987 × 20 $0.987 \times 0.987 \times 20$  mm3 crystal columns, respectively. Monte Carlo simulations of our Prism-PET scanners, Siemens Biograph Vision, and United Imaging EXPLORER were performed using Geant4 application for tomographic emission (GATE). National Electrical Manufacturers Association (NEMA) standard was followed for the evaluation of spatial resolution, sensitivity, and count-rate performance. An ultra-micro hot spot phantom was simulated for assessing image quality. A modified Zubal brain phantom was utilized for radiotracer imaging simulations of 5-HT1A receptors, which are abundant in the raphe nuclei (RN), and norepinephrine transporters, which are highly concentrated in the bilateral locus coeruleus (LC). RESULTS: The Prism-PET brain scanner with 1.5 mm crystals is superior to that with 1 mm crystals as the former offers better depth-of-interaction (DOI) resolution, which is key to realizing compact and conformal PET scanner geometries. We achieved uniform 1.3 mm full-width-at-half-maximum (FWHM) spatial resolutions across the entire transaxial field-of-view (FOV), a NEMA sensitivity of 52.1 kcps/MBq, and a peak noise equivalent count rate (NECR) of 957.8 kcps at 25.2 kBq/mL using 450-650 keV energy window. Hot spot phantom results demonstrate that our scanner can resolve regions as small as 1.35 mm in diameter at both center and 10 cm away from the center of the transaixal FOV. Both 5-HT1A receptor and norepinephrine transporter brain simulations prove that our Prism-PET scanner enables accurate quantification of radiotracer uptake in small brain regions, with a 1.8-fold and 2.6-fold improvement in the dorsal RN as well as a 3.2-fold and 4.4-fold improvement in the bilateral LC compared to the Biograph Vision and EXPLORER, respectively. CONCLUSIONS: Based on our simulation results, the proposed high-resolution and high-sensitivity Prism-PET brain scanner is a promising cost-effective candidate to achieve quantitative molecular neuroimaging of small but important brain regions with PET clinically viable.

Metabolic positron-emission tomography/magnetic resonance imaging in primary progressive aphasia and frontotemporal lobar degeneration subtypes: Reassessment of expected [18F]-fluorodeoxyglucose uptake patterns.

Clinical assessment of frontotemporal lobar degeneration (FTLD)/primary progressive aphasia (PPA) patients is challenging, given that common cognitive assessments rely extensively on language. Since asymmetry in neuroimaging biomarkers is often described as a central finding in these patients, our study evaluated [18F]-fluorodeoxyglucose (FDG) uptake patterns in patients meeting clinical and imaging criteria for FTLD, with emphasis on PPA. Fifty-one subjects underwent brain [18F]-FDG positron-emission tomography/magnetic resonance imaging (PET/MRI) as part of their routine clinical workup for dementia and neurodegenerative disease. Images were obtained using a Siemens Biograph mMR integrated 3T PET/MRI scanner. PET surface maps and fusion fluid-attenuated inversion recovery-PET images were generated utilizing MIMneuro software. Two board-certified neuroradiologists and one nuclear medicine physician blinded to patient history classified each FTLD/PPA subtype and assessed for left- versus right-side dominant hypometabolism. Qualitative and semiquantitative assessment demonstrated 18 cases of PPA, 16 behavioral variant frontotemporal dementia (bvFTD), 12 corticobasal degeneration, and 5 progressive supranuclear palsy. Among the 18 PPA subjects (11 svPPA, 5 lvPPA, and 2 agPPA), 12 (67%) demonstrated left-dominant hypometabolism and 6 (33%) right-dominant hypometabolism. While existing literature stresses left-dominant hypometabolism as a key imaging feature in the PPA subtypes, a third of our cases demonstrated right-dominant hypometabolism, suggesting that emphasis should be placed on the functionality of specific brain regions affected, rather than left versus right sidedness of hypometabolism patterns.

Fluorodeoxyglucose positron-emission tomography-magnetic resonance hybrid imaging: An emerging tool for staging of cancer of the uterine cervix.

Positron-emission tomography-magnetic resonance imaging (PET-MRI) is an emerging hybrid imaging modality that utilizes the superior soft tissue resolution of MR with the metabolic data from PET. In this study, we sought to assess the clinical value of fluorodeoxyglucose (FDG) PET-MRI with dedicated pelvic PET-MR in the initial staging of cervical cancer. In this institutional-approved study, we identified 23 adult females who underwent FDG PET-MRI on hybrid camera for staging of primary uterine cervical cancer that included a dedicated PET-MR of the pelvis. A nuclear medicine physician and a radiologist reviewed the PET, MRI, and fusion-body and pelvis images alone and then with consensus read characterizing PET and MR abnormal findings. There were 23 patients who underwent FDG PET-MRI for initial staging of cervical cancer with an average age of 52.2 ± 14.0 years. A total of 23 suspected lymph nodes in eight different patients were detected within the pelvis with increased metabolic activity on PET. Both the dedicated pelvis and whole-body PET imaging detected the same corresponding pelvic lymph nodes, although the pelvic PET imaging had better lymph node uptake delineation due to longer acquisition time. Using a 10-mm short-axis criterion, MRI identified only 43.5% of the FDG avid lymph nodes. The average SUVmax on the pelvis PET sequences was higher with SUV 8.9 ± 5.2 compared to the whole-body PET with SUV 7.8 ± 5.4 but was not statistically significant (P > 0.05). Primary cervical cancer was identified in 18 patients on both PET imaging and MRI with dedicated MR pelvis providing better characterization. Based on our results of the patients with cervical cancer evaluated for initial staging, combining dedicated pelvic PET-MRI with whole-body PET/MR provides the most complete status of malignant disease in reference to delineation of primary tumor, involvement of surrounding tissues, and regional lymph nodes.

(18F)-Fluorodeoxyglucose positron emission tomography/magnetic resonance imaging assessment of hypometabolism patterns in clinical phenotypes of suspected corticobasal degeneration.

Corticobasal degeneration (CBD) is a rare neurodegenerative disorder presenting with atypical parkinsonian symptoms that characteristically involves the frontoparietal region including the primary sensorimotor cortex, ipsilateral basal ganglia, and thalamus, typically in an asymmetric pattern. We aim to evaluate the metabolic and volumetric abnormalities in patients with clinically suspected CBD phenotypes utilizing hybrid 18F-fluorodeoxyglucose (FDG) positron emission tomography-magnetic resonance (PET/ MR) brain imaging. A retrospective analysis was performed on 75 patients (mean age 74 years, 31 males and 44 females) who underwent 18F-FDG PET/MR imaging (MRI) as part of their clinical dementia workup. Images were obtained using an integrated Siemens mMR 3T PET/MRI scanner. Two board-certified neuroradiologists and a nuclear medicine physician evaluated the metabolic and volumetric data of each hemisphere to assess for symmetric or asymmetric involvement of regions of interest in the subset of patients with suspected CBD. Of the 75 patients, 12 were diagnosed with suspected CBD based on a combination of clinical symptoms, neurocognitive testing, and hybrid neuroimaging findings. Ten of 12 patients (87%) demonstrated asymmetrically decreased FDG uptake involving a single cerebral hemisphere and ipsilateral subcortical structures, whereas two of 12 patients (13%) demonstrated striking hypometabolism of the bilateral sensorimotor cortices. Our study highlights two characteristic patterns of hypometabolism in patients with clinical and neuroimaging findings suggestive of the underlying CBD. The first pattern is asymmetric hypometabolism and volume loss, particularly within the frontoparietal and occipital cortices with involvement of ipsilateral subcortical structures, including the basal ganglia and thalamus. The second, more atypical pattern, is symmetric hypometabolism with striking involvement of the bilateral sensorimotor cortices.

Hybrid imaging in dementia: A semi-quantitative (18F)-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging approach in clinical practice.

Neurodegenerative disorders may demonstrate typical lobar and regional patterns of volume loss with corresponding decreased glucose metabolism. In this retrospective study, we correlated semi-quantitative volumetric changes utilizing NeuroQuant morphometric analysis with decreased fluorodeoxyglucose (FDG) uptake age-matched calculated z-scores utilizing 18F-FDG positron emission tomography/magnetic resonance imaging (PET/MRI). Eighty-nine patients (mean age 71.4) with clinical findings suggestive of various subtypes of dementia underwent PET/MR brain imaging. Cases were categorized as follows: Alzheimer's dementia (AD), frontotemporal lobar degeneration (FTLD), dementia with Lewy bodies (DLB), and corticobasal degeneration (CBD). NeuroQuant software provided semi-quantitative assessment of lobar-specific patterns of volume loss compared to age-matched controls. MIMneuro software provided semi-quantitative FDG uptake data, with metabolic z-scores generated in comparison to age-matched controls. Volumetric and metabolic data were then correlated for statistical significance. In 29 AD cases, Pearson correlation coefficient between z-score and lobar volume was 0.3 (P = 0.120) and 0.38 (P < 0.05), for parietal and temporal lobes, respectively. In 34 FTLD cases, it was 0.35 (P = 0.051) and 0.02 (P = 0.916), for frontal and temporal lobes, respectively. In 14 DLB cases, it was 0.42 (P = 0.130), 0.5 (P = 0.067), and 0.22 (P = 0.447) for the occipital lobes, middle occipital gyrus, and parietal lobes, respectively. In 12 CBD cases, it was 0.58 (P < 0.05) for the superior parietal lobule. Semi-quantitative (F18)-FDG PET/MRI analysis demonstrated a positive relationship between volumetric loss and hypometabolism within certain lobar-specific regions, depending on neurodegenerative disorder subtype. Our findings may add diagnostic confidence in the accurate imaging diagnosis of neurodegenerative disease.

FDG PET/MRI for Visual Detection of Crossed Cerebellar Diaschisis in Patients With Dementia.

OBJECTIVE: Depressed regional metabolism and cerebellar blood flow may be caused by dysfunction in anatomically separate but functionally related regions, presumably related to disruption of the corticopontine-cerebellar pathway. The purpose of this study was to evaluate the prevalence of crossed cerebellar diaschisis (CCD) in patients undergoing 18F-FDG PET/MRI for suspected neurodegenerative disease. MATERIALS AND METHODS: In total, 75 patients (31 men, 44 women; mean age, 74 years) underwent hybrid FDG PET/MRI for clinical workup of neurodegenerative disease. Images were obtained with an integrated 3-T PET/MRI system. PET surface maps, fused T1-weighted magnetization-prepared rapid acquisition gradient echo and axial FLAIR/PET images were generated with postprocessing software. Two board-certified neuroradiologists and a nuclear medicine physician blinded to patient history evaluated for pattern of neurodegenerative disease and CCD. RESULTS: Qualitative assessment showed that 10 of 75 (7.5%) patients had decreased FDG activity in the cerebellar hemisphere contralateral to the supratentorial cortical hypometabolism consistent with CCD. Six of the 10 patients had characteristic imaging findings of frontotemporal dementia (three behavioral variant frontotemporal dementia, two semantic primary progressive aphasia, and one logopenic primary progressive aphasia), three had suspected corticobasal degeneration, and one had Alzheimer dementia. CONCLUSION: Our study results suggest that CCD occurs most commonly in frontotemporal dementia, particularly the behavioral variant, and in patients with cortico-basal degeneration. Careful attention to cerebellar metabolism may assist in the clinical evaluation of patients with cognitive impairment undergoing FDG PET/MRI as part of their routine dementia workup.

Incidental PET/CT Findings of Suspected COVID-19 in a Region of High Prevalence.

We describe a case of suspected COVID-19 pneumonia in a 61-year-old male with known primary central nervous system diffuse large B-cell lymphoma (DLBCL) who underwent restaging PET/CT during the initial peak of infection of COVID-19 pneumonia within the New York region. At the time of his routine PET-CT to assess for disease progression, typical CT imaging features of COVID-19 pneumonia were identified. Upon further investigation, the patient was asymptomatic, and his infection status remained unknown. He was subsequently lost to follow-up with his COVID-19 status pending.

Initial Studies with 11C-Vorozole PET Detect Overexpression of Intratumoral Aromatase in Breast Cancer.

Aromatase inhibitors are the mainstay of hormonal therapy in estrogen receptor-positive breast cancer, although the response rate is just over 50% and in vitro studies suggest that only two thirds of postmenopausal breast tumors overexpress aromatase. The goal of the present study was to validate and optimize PET with 11C-vorozole for measuring aromatase expression in postmenopausal breast cancer in vivo. Methods: Ten newly diagnosed postmenopausal women with biopsy-confirmed breast cancer were administered 11C-vorozole intravenously, and PET emission data were collected between 40 and 90 min after injection. Tracer injection and scanning were repeated 2 h after ingestion of 2.5 mg of letrozole. Mean and maximal SUVs and ratios to nontumor tissue in the contralateral breast were determined at baseline and after letrozole. Biopsy specimens from the same tumors were stained for aromatase using immunohistochemistry and evaluated for stain intensity and the percentage of immune-positive cells. Results: Seven of the 10 women (70%) demonstrated increased mean focal uptake of tracer (SUV ratio > 1.1) coinciding with the mammographic location of the lesion, whereas the other 3 women (30%) did not (SUV ratio ≤ 1.0). All patients with an SUV ratio above 1.1 had mean SUVs above 2.4, and there was no overlap (SUV ratio ≤ 1; SUVmean, 0.8-1.8). The SUV ratio relative to breast around tumor was indistinguishable from the ratio to contralateral breast. Pretreatment with letrozole reduced tracer uptake in most subjects, although the percentage of blocking varied across and within tumors. Tumors with a high SUV in vivo also showed a high immunohistochemical staining intensity. Conclusion: PET with 11C-vorozole is a useful technique for measuring aromatase expression in individual breast lesions, enabling noninvasive quantitative measurement of baseline and posttreatment aromatase availability in primary tumors and metastatic lesions.

Added Value of Including Entire Brain on Body Imaging With FDG PET/MRI.

OBJECTIVE: FDG PET/MRI examination of the body is routinely performed from the skull base to the mid thigh. Many types of brain abnormalities potentially could be detected on PET/MRI if the head was included. The objective of this study was therefore to identify and characterize brain findings incidentally detected on PET/MRI of the body with the head included. MATERIALS AND METHODS: We retrospectively identified 269 patients with FDG PET/MRI whole-body scans that included the head. PET/MR images of the brain were reviewed by a nuclear medicine physician and neuroradiologist, first individually and then concurrently. Both PET and MRI findings were identified, including abnormal FDG uptake, standardized uptake value, lesion size, and MRI signal characteristics. For each patient, relevant medical history and prior imaging were reviewed. RESULTS: Of the 269 subjects, 173 were women and 96 were men (mean age, 57.4 years). Only the initial PET/MR image of each patient was reviewed. A total of 37 of the 269 patients (13.8%) had abnormal brain findings noted on the PET/MRI whole-body scan. Sixteen patients (5.9%) had vascular disease, nine patients (3.3%) had posttherapy changes, and two (0.7%) had benign cystic lesions in the brain. Twelve patients (4.5%) had serious nonvascular brain abnormalities, including cerebral metastasis in five patients and pituitary adenomas in two patients. Only nine subjects (3.3%) had a new neurologic or cognitive symptom suggestive of a brain abnormality. CONCLUSION: Routine body imaging with FDG PET/MRI of the area from the skull base to the mid thigh may miss important brain abnormalities when the head is not included. The additional brain abnormalities identified on whole-body imaging may provide added clinical value to the management of oncology patients.

18F-FDG PET-CT: predicting recurrence in patients following percutaneous cryoablation treatment for stage I primary non-small-cell lung cancer.

PURPOSE: The aim of this study was to understand the imaging features of fluorine-18 fluorodeoxyglucose ((18)F-FDG) PET-computed tomography (CT) in postcryoablation lung cancer patients that could help predict recurrence. METHODS: We identified 28 patients with 30 lesions treated by means of percutaneous cryoablation for stage I non-small-cell lung cancer. Two experienced nuclear radiologists blindly reviewed baseline images and follow-up (18)F-FDG PET-CT scans for a minimum of 24 months, with discrepancy in interpretation resolved by consensus. Nineteen lesions had undergone baseline PET-CT studies, whereas 11 lesions had undergone only baseline CT studies. Follow-up PET-CT studies were analyzed for up to 24 months, whereas the recurrence-free survival analysis was performed for 36 months. RESULTS: The average maximum standardized uptake value (SUV(max)) at baseline (n = 19) was 5.2 ± 3.9 and the average CT area at baseline was 2.2 ± 1.6 cm(2). Only the CT area was significantly different between recurring and nonrecurring lesions at baseline (P = 0.0028). The Kaplan-Meier survival analysis showed that dichotomizing lesions around 2 cm on CT did not result in a statistically significant survival difference (hazard ratio = 1.42, 95% confidence interval: 0.63-2.21). The average SUV(max) at first follow-up was 1.9 ± 1.8 for 27 lesions, whereas the average SUV(max) of recurrent lesions was 2.2 ± 2.2 and that of nonrecurrent lesions was 1.5 ± 0.3 (P = 0.17). Six lesions had SUV(max) more than or equal to 2.5 within 24 months, all of which recurred in the ablation zone. CONCLUSION: (18)F-FDG PET-CT is a valuable tool for determining treatment response and for distinguishing benign from malignant lesions after cryoablation. The CT area was most predictive of future recurrence at baseline, whereas SUV(max) more than or equal to 2.5 was most predictive of future recurrence at first follow-up.