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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 88FDG 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.

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.

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.

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.

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.

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.Two Prism-PET brain scanner setups were proposed based on our 4-to-1 and 9-to-1 coupling of scintillators to readout pixels usingThe 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-HTBased 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.

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 (11)C-vorozole for measuring aromatase expression in postmenopausal breast cancer in vivo. Methods: Ten newly diagnosed postmenopausal women with biopsy-confirmed breast cancer were administered (11)C-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; SUV(mean), 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 (11)C-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.

Ventilation/perfusion tomography (V/P SPECT) is recommended as the firsthand tool for diagnosis of pulmonary embolism (PE) based on standardized technology and new holistic interpretation criteria. Pre-test probability helps clinicians to choose the most appropriate objective test for diagnosis or exclusion of PE. Interpretation takes into account all ventilation and perfusion patterns allowing for diagnosis of other cardiopulmonary diseases than PE. In such contexts, V/P SPECT has both an excellent sensitivity and an excellent specificity for detecting PE. V/P SPECT has no contraindication; it is noninvasive and radiation exposure is low. Moreover, acquisition time for V/P SPECT is only 20 min. It allows for quantification of PE extension, which has an impact on individual treatment. It is uniquely useful for a clinical follow-up and for research.

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 undergoingIn 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.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.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.

High-resolution PET imaging has considerable potential to improve management of breast cancer, especially if it could be acquired simultaneously with the clinical standard of breast MRI. In this multimodal approach, PET contributes critical information on specific molecular subtypes and heterogeneity, while avoiding the challenge of reproducibly positioning the breast which confronts technologists when PET and MRI images are acquired separately. Using a compact, high-resolution and MR-compatible PET system (VersaPET) mounted into a breast MRI table, we have begun to assess the feasibility of this approach by collecting preliminary FDG data on primary tumors in breast cancer patients. In order to augment this approach to examine nodal involvement, we also performed a simulation study that incorporates novel detector geometries to expand the FOV to include axillary lymph nodes which are critical for diagnosing metastasis. We evaluated scanner geometries with limited angle sampling and features including time of flight (TOF) and depth of interaction (DOI) readouts, using GATE simulation and detection-based tasks using channelized Hotelling observer (CHO). Our simulation result indicates superior performance for detection of low-grade (3:1 lesion to tissue contrast), small (3 mm diameter) lesions using the proposed scanners compared to whole-body PET. We show that the incorporation of a DOI resolution of 2 mm substantially improves the detection tasks for the proposed scanner designs, while TOF capability is less impactful.

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.

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.

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.

Cognitive and constitutional symptomatology is common in cancer patients but the causes are not well understood. To investigate whether cancers cause these symptoms by changing cerebral metabolism, we measured the cerebral rate of glucose consumption (CMRglc) in patients diagnosed with a lung lesion.MethodsThe CMRglc was quantified in 20 patients undergoing 18F-FDG PET for lesion staging. The cognitive status was assessed by neuropsychological testing.ResultsParadoxically, despite being alert three of the patients had CMRglc typical of people who are in deep sleep or anesthetized. All three had cancers, two died within 2 months of scanning. Remaining patients including four with early stage cancer had CMRglc within normal range.ConclusionsWe speculate that the low CMRglc reflects a switch to an alternative energy source that is mediated by cancers remotely. Identifying the underlying mechanism and the alternative energy sources may help to understand how cancers can change body metabolism.

The recent explosion in development of new radiotracers for cancer diagnosis and targeted therapy, many of which target biomolecules, which vary in abundance as a function of hormonal milieu, poses a disproportionate risk of adverse effects in women of reproductive age.

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.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.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.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.

Primary hyperoxaluria is a rare congenital disorder of abnormal glyoxylate metabolism with resultant over-accumulation of oxalate, which then binds with calcium and precipitates in the kidneys, resulting in nephrocalcinosis and nephrourolithiasis. As renal function worsens, patients develop systemic oxalosis with calcium oxalate deposition in the soft tissues, musculoskeletal system, cardiovascular system, central nervous system, and eyes [1–5]. There are three common types of primary hyperoxaluria (types I–III). Type I is the most common and severe and involves a mutation in the alanine glyoxylate aminotransferase (AGT) enzyme causing overproduction of oxalate glyoxylate [1]. Type II results from deficiency of glyoxylate reductase and hydroxypyruvate reductase (GRHPR), which results in overproduction of oxalate and L-glyceric aciduria [1, 5]. Type III results from mutation in 4-hydroxy-2oxoglutarate aldolase (HOGA) and is the least aggressive hyperoxaluria type, with most patients not progressing to end-stage renal disease (ESRD) [1]. Imaging findings in primary hyperoxaluria vary depending on patient age and renal function [2–6]. Prior to renal function impairment, imaging is frequently normal. As renal failure develops, cortical nephrocalcinosis and nephrourolithiasis will be seen (Fig. 1). Calcium oxalate subsequently deposits in soft tissues, tendons, and joint capsules, with joint effusions and nodular-appearing tumoral calcinosis (especially in periarticular regions, which can cause erosive arthropathy) [2–6]. As ESRD develops toward the late stage of the disease, musculoskeletal imaging manifestations typically associated with renal osteodystrophy and secondary hyperparathyroidism will develop, such as osteosclerosis, subperiosteal resorption, Brugger-jersey^ spine, and vascular/soft tissue calcifications (also seen in Fig. 1). Abnormal skeletal maturation and pathologic fractures with delayed healing can also be seen but are similarly nonspecific. Oxalate deposition in the subcutaneous and dermal tissues can cause skin necrosis/ulceration, and oxalate deposition in the myocardium, pericardium, ocular and vascular regions has also been described [4–9]. Skeletal findings more specific to primary hyperoxaluria may include irregular diametaphyseal transverse sclerotic bands and wide metaphyseal zones [5]. Lytic lesions can be seen in primary hyperoxaluria, which histopathologically represent foci of calcium oxalate deposition with a granulomatous foreign body histiocytic reaction, which appear essentially identical to brown tumors on The case presentation can be found at doi: 10.1007/s00256-015-2161-1.

ObjectivesThe aim of this study was to evaluate the prognostic value of pretreatment 18F-fluorodeoxyglucose PET/computed tomography (CT), particularly in the assessment of metabolic tumor burden markers such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG), with respect to clinical

Clorgyline is an irreversible inhibitor of monoamine oxidase (MAO A) which has been labeled with carbon-11 (C-11) and used to measure human brain MAO A with positron emission tomography (PET). In this study we compared [11C]clorgyline and deuterium-substituted [11C]clorgyline ([11C]clorgyline-D2) to better understand the molecular link between [11C]clorgyline binding and MAO A. In PET studies of five normal healthy volunteers scanned with [11C]clorgyline and [11C]clorgyline-D2 2 h apart, deuterium substitution generally produced the expected reductions in the brain uptake of [11C]clorgyline. However, the reduction was not uniform with the C-11 binding in white matter being significantly less sensitive to deuterium substitution than other brain regions. The percentages of the total binding attributable to MAO A is largest for the thalamus and smallest for the white matter and this is clearly seen in PET images with [11C]clorgyline-D2. Thus deuterium-substituted [11C]clorgyline selectively reduces the MAO A binding component of clorgyline in the human brain revealing non-MAO A binding which is most apparent in the white matter. The characterization of the non-MAO A binding component of this widely used MAO A inhibitor merits further investigation.

One of the major mechanisms for terminating the actions of catecholamines and vasoactive dietary amines is oxidation by monoamine oxidase (MAO). Smokers have been shown to have reduced levels of brain MAO, leading to speculation that MAO inhibition by tobacco smoke may underlie some of the behavioral and epidemiological features of smoking. Because smoking exposes peripheral organs as well as the brain to MAO-inhibitory compounds, we questioned whether smokers would also have reduced MAO levels in peripheral organs. Here we compared MAO B in peripheral organs in nonsmokers and smokers by using positron emission tomography and serial scans with the MAO B-specific radiotracers, l -[ 11 C]deprenyl and deuterium-substituted l -[ 11 C]deprenyl ( l -[ 11 C]deprenyl-D2). Binding specificity was assessed by using the deuterium isotope effect. We found that smokers have significantly reduced MAO B in peripheral organs, particularly in the heart, lungs, and kidneys, when compared with nonsmokers. Reductions ranged from 33% to 46%. Because MAO B breaks down catecholamines and other physiologically active amines, including those released by nicotine, its inhibition may alter sympathetic tone as well as central neurotransmitter activity, which could contribute to the medical consequences of smoking. In addition, although most of the emphases on the carcinogenic properties of smoke have been placed on the lungs and the upper airways, this finding highlights the fact that multiple organs in the body are also exposed to pharmacologically significant quantities of chemical compounds in tobacco smoke.

Monoamine oxidase (MAO) catalyzes the oxidative deamination of many biogenic and dietary amines. Though studies of MAO have focused mainly on its regulatory role in the brain, MAO in peripheral organs also represents a vast mechanism for detoxifying vasoactive compounds as well as for terminating the action of physiologically active amines, which can cross the blood brain barrier. Indeed, robust central and peripheral MAO activity is a major requirement in the safe use of many CNS drugs, particularly antidepressants, and thus an awareness of the MAO inhibitory potential of drugs is essential in therapeutics. In this study, we examined the feasibility of quantifying MAO A in peripheral organs in healthy human subjects using comparative positron emission tomography (PET) imaging with carbon-11 (t1/2: 20.4 min) labeled clorgyline ([11C]clorgyline) a suicide inactivator of MAO A and its deuterium labeled counterpart ([11C]clorgyline-D2). Heart, lungs, kidneys, thyroid, and spleen showed a robust deuterium isotope effect characteristic of MAO and the magnitude of the effect was similar to that of trancylcypromine, an irreversible MAO inhibitor used in the treatment of depression. Liver time-activity curves were not affected by deuterium substitution precluding the estimation of liver MAO in vivo. In organs showing an isotope effect, MAO A is greatest in the lungs and kidneys followed by the thyroid and heart. This method, which has been previously applied in the human brain, opens the possibility to also directly assess the effects of different variables including smoking, dietary substances, drugs, disease, and genetics on peripheral MAO A in humans. Synapse 49:178–187, 2003. Published 2003 Wiley-Liss, Inc.

Two patients demonstrated an unusual pattern of intense bone and surrounding soft tissue hypermetabolic uptake in the posterior pelvis on fluorodeoxyglucose positron emission tomography with computed tomography PET-CT scans. After further investigation, we found that both patients underwent uncomplicated autologous bone marrow harvesting several weeks before imaging. These two cases illustrate a distinctive PET-CT appearance following bone marrow harvesting that the radiologist needs to recognize to not confuse the findings with metastatic disease.

Methylphenidate (Ritalin) is an effective drug in the treatment of attention deficit hyperactivity disorder. However, the doses required therapeutically vary significantly between subjects and it is not understood what determines these differences. Since methylphenidate's therapeutic effects are in part due to increases in extracellular DA secondary to blockade of dopamine transporters (DAT), the variability could reflect differences in levels of DAT blockade. Here we used PET to assess if for a given dose of methylphenidate the differences in DAT blockade account for the variability in methylphenidate-induced increases in extracellular DA. Ten healthy adult subjects were tested before and 60 min after oral methylphenidate (60 mg) with PET to estimate DAT occupancy (with [(11)C]cocaine as the radioligand) and levels of extracellular DA (with [(11)C]raclopride as the D2 receptor radioligand that competes with endogenous DA for binding to the receptor). Methylphenidate significantly blocked DAT (60 +/- 11%) and increased extracellular DA in brain (16 +/- 8% reduction in [(11)C]raclopride binding in striatum). However, the correlation between methylphenidate-induced DAT blockade and DA increases was not significant. These results indicate that for a given dose of methylphenidate, individual differences in DAT blockade are not the main source for the intersubject variability in MP-induced increases in DA. This finding suggests that individual differences in response to MP are due in part to individual differences in DA release, so that for an equivalent level of DAT blockade, MP would induce smaller DA changes in subjects with low than with high DA cell activity.

Hepatobiliary radionuclide imaging is typically performed to detect cholecystitis. Infrequently, imaging reveals an obstructive pattern. Although delayed hepatobiliary imaging is commonly used to differentiate between intrahepatic (IH) and extrahepatic (EH) obstruction in the newborn; there is room to clarify the use of delayed imaging in the adult population. A retrospective review was performed of adult patients demonstrating a complete obstructive pattern on initial Tc-99m mebrofenin hepatobiliary imaging. Delayed imaging was divided into early delayed (ED) (

The role of dopamine in the addictive process (loss of control and compulsive drug intake) is poorly understood. A consistent finding in drug-addicted subjects is a lower level of dopamine D2 receptors. In cocaine abusers, low levels of D2 receptors are associated with a lower level of metabolism in the orbitofrontal cortex. Because the orbitofrontal cortex is associated with compulsive behaviors, its disruption may contribute to compulsive drug intake in addicted subjects. This study explored whether a similar association occurs in methamphetamine abusers.Fifteen methamphetamine abusers and 20 non-drug-abusing comparison subjects were studied with positron emission tomography (PET) and [11C]raclopride to assess the availability of dopamine D2 receptors and with [18F]fluorodeoxyglucose to assess regional brain glucose metabolism, a marker of brain function.Methamphetamine abusers had a significantly lower level of D2 receptor availability than comparison subjects (a difference of 16% in the caudate and 10% in the putamen). D2 receptor availability was associated with metabolic rate in the orbitofrontal cortex in abusers and in comparison subjects.Lower levels of dopamine D2 receptor availability have been previously reported in cocaine abusers, alcoholics, and heroine abusers. This study extends this finding to methamphetamine abusers. The association between level of dopamine D2 receptors and metabolism in the orbitofrontal cortex in methamphetamine abusers, which replicates previous findings in cocaine abusers, suggests that D2 receptor-mediated dysregulation of the orbitofrontal cortex could underlie a common mechanism for loss of control and compulsive drug intake in drug-addicted subjects.

Objective: Methamphetamine has raised concerns because it may be neurotoxic to the human brain. Although prior work has focused primarily on the effects of methamphetamine on dopamine cells, there is evidence that other neuronal types are affected. The authors measured regional brain glucose metabolism, which serves as a marker of brain function, to assess if there is evidence of functional changes in methamphetamine abusers in regions other than those innervated by dopamine cells. Method: Fifteen detoxified methamphetamine abusers and 21 comparison subjects underwent positron emission tomography following administration of [ 18 F]fluorodeoxyglucose. Results: Whole brain metabolism in the methamphetamine abusers was 14% higher than that of comparison subjects; the differences were most accentuated in the parietal cortex (20%). After normalization for whole brain metabolism, methamphetamine abusers exhibited significantly lower metabolism in the thalamus (17% difference) and striatum (where the differences were larger for the caudate [12%] than for the putamen [6%]). Statistical parametric mapping analyses corroborated these findings, revealing higher metabolism in the parietal cortex and lower metabolism in the thalamus and striatum of methamphetamine abusers. Conclusions: The fact that the parietal cortex is a region devoid of any significant dopaminergic innervation suggests that the higher metabolism seen in this region in the methamphetamine abusers is the result of methamphetamine effects in circuits other than those modulated by dopamine. In addition, the lower metabolism in the striatum and thalamus (major outputs of dopamine signals into the cortex) is likely to reflect the functional consequence of methamphetamine in dopaminergic circuits. These results provide evidence that, in humans, methamphetamine abuse results in changes in function of dopamine- and nondopamine-innervated brain regions.

The route of administration influences the reinforcing effects of cocaine. Here we assessed whether there were differences in the efficacy of cocaine to block the dopamine transporters (major target for cocaine's reinforcing effects), as a function of route of administration. Positron emission tomography and [11C]cocaine, a dopamine transporter radioligand, were used to compare the levels of dopamine transporter blockade induced by intravenous, smoked and intranasal cocaine in 32 current cocaine abusers. In parallel, the temporal course for the self-reports of "high" were obtained. Cocaine significantly blocked dopamine transporters. The levels of blockade were comparable across all routes of administration and a dose effect was observed for intravenous and intranasal cocaine but not for smoked cocaine. For equivalent levels of cocaine in plasma and DAT blockade, smoked cocaine induced significantly greater self reports of "high" than intranasal cocaine and showed a trend for a greater effect than intravenous cocaine. The time to reach peak subjective was significantly faster for smoked (1.4+/-0.5 min) than for intravenous cocaine (3.1+/-0.9 min), which was faster than intranasal cocaine (14.6+/-8 min). Differences in the reinforcing effects of cocaine as a function of the route of administration are not due to differences in the efficacy of cocaine to block the dopamine transporters. The faster time course for the subjective effects for smoked than intravenous and for intravenous than for intranasal cocaine highlights the importance of the speed of cocaine's delivery into the brain on its reinforcing effects.

Background: Ethanol has a broad range of actions on many neurotransmitter systems. The depressant actions of ethanol in the brain are related in part to facilitation of γ-aminobutyric acid (GABA) neurotransmission via its interaction with the benzodiazepine/GABA receptor complex. The purpose of this study was to evaluate the effects of ethanol on regional brain metabolism in 10 healthy right-handed men. The results were compared with those we previously published in a different group of 16 normal male subjects who received intravenous lorazepam, a benzodiazepine drug that also enhances GABA neutrotranmission. Methods: The subjects were scanned with positron emission tomography and [F-18] fluorodeoxyglucose twice: 40 min after the end of placebo (diet soda) or ethanol (0.75 g/kg) oral administration. Image data sets were analyzed by using both the region of interest and the statistical parametric mapping (SPM) approach. SPM was used to generate a difference image between baseline and ethanol, which we compared to the difference image between baseline and lorazepam (30 μg/kg). Results: Ethanol significantly increased self-reports of high (p≤ 0.0001), dizziness (p≤ 0.004), and intoxication (p≤ 0.0001). Ethanol significantly decreased whole brain (-25 ±6%,p≤ 0.0001) and regional metabolism. Normalization of the regional measures by whole brain metabolism (relative measures) showed that ethanol decreased relative metabolic activity in occipital cortex (-4.9 ± 4.1%, p ≤ 0.006), whereas it increased relative metabolic act in left temporal cortex (+3.5 ± 2.9%, p≤ 0.006) and left basal ganglia (+9 ± 6.3%, p≤ 0.0009). SPM analyses revealed the same pattern of responses as the relative measures, showing decreases in occipital cortex and increases in left temporal cortex. Comparison of the relative measures and the SPM analyses obtained with lorazepam data revealed a similar pattern of effects, with relative decreases in occipital cortex (-7.8 ± 4.8%) and relative increases in left temporal cortex (+3.8 ± 5.7%). Lorazepam, but not ethanol, also decreased thalamic metabolism (-11.2 ± 7.2%). Conclusions: These results support similar though not identical mechanisms for the effects of alcohol and benzodiazepines on brain glucose metabolism. The fact that lorazepam, but not alcohol, reduced thalamic metabolism, an effect associated with sleepiness, could explain the higher sedative effects of lorazepam than of alcohol.

Background: It has been reported that acute ethanol intoxication decreases the brain water proton magnetic resonance T 1 values, an effect that has been interpreted to indicate brain dehydration during this condition. Because water macromolecular interactions largely determine tissue water T 1 , another possible explanation for reduced brain water proton T 1 values is that the interaction between water and brain macromolecules is altered by ethanol. Methods: A 4.0 T magnetic resonance imaging (MRI) instrument was used to measure brain water proton T 1 relaxation times before, during, and after ethanol intoxication (dose, 0.75 mg/kg) in healthy controls. Results: The T 1 relaxation times as assessed with MRI were highly reproducible. The mean, paired ethanol-induced differences in T 1 were -0.004 ± 0.007 sec (mean ± standard deviation) for white matter and 0.010 ± 0.015 sec for internal gray matter structures, neither of which was significant. Conclusions: This reasonably sensitive measurement does not support the view that tissue water content or water macromolecule interactions are significantly altered in the brain during acute alcohol intoxication in otherwise healthy subjects.

MRI is a major tool for mapping brain function; thus it is important to assess potential effects on brain neuronal activity attributable to the requisite static magnetic field. This study used positron emission tomography (PET) and (18)F-deoxyglucose ((18)FDG) to measure brain glucose metabolism (a measure of brain function) in 12 subjects while their heads were in a 4 T MRI field during the (18)FDG uptake period. The results were compared with those obtained when the subjects were in the earth's field (PET scanner), and when they were in a simulated MRI environment in the PET instrument that imitated the restricted visual field of the MRI experiment. Whole-brain metabolism, as well as metabolism in occipital cortex and posterior cingulate gyrus, was lower in the real (4 T) and simulated (0 T) MRI environments compared with the PET. This suggests that the metabolic differences are due mainly to the visual field differences characteristic of the MRI and PET instruments. We conclude that a static magnetic field of 4 T does not in itself affect this fairly sensitive measure of brain activity.

Positron emission tomography (PET) studies with [11C]L-deprenyl-D2 have shown that brain monoamine oxidase (MAO) B is 40% lower in smokers than in non-smokers. Here we investigated whether MAO B inhibition can be detected after smoking a single cigarette. Eight normal healthy non-smokers (35 +/- 11 years) received two PET studies 2 h apart with [11C]L-deprenyl-D2, one at baseline and the second 5-10 min after the subject had smoked a single cigarette. Plasma nicotine and expired carbon monoxide (CO) were measured prior to smoking and 10 min after smoking completion as an index of tobacco smoke exposure. A three-compartment model was used to calculate lambda k3, a model term which is proportional to MAO B activity and which is derived from the time course of carbon-11 in the brain and the time course of the radiotracer in the plasma and K1, the plasma-to-brain transfer constant (for [11C]L-deprenyl-D2) which is related to brain blood flow. Subjects experienced difficulty inhaling and became dizzy and/or nauseous after smoking. Plasma nicotine averaged 11.6 +/- 5.5 ng/ml and expired CO averaged 8 +/- 10 ppm after smoking. The average lambda k3 and K1 for 11 different brain regions did not differ significantly between baseline and smoking. These results indicate that the reduction in MAO B in smokers probably occurs gradually and requires chronic tobacco smoke exposure.

Though the blockade of dopamine transporters (DAT) is associated with cocaine's and methylphenidate's reinforcing effects, it is the stimulation of dopamine (DA) receptors, achieved by increases in synaptic DA, that enables these effects to occur. Positron emission tomography (PET) and [11C]raclopride were used to assess the levels of occupancy of DA D2 receptors by dopamine achieved by doses of cocaine or methylphenidate previously documented to block over 70% of DAT. Studies were performed in five baboons using a paired scan protocol designed to measure DA D2 receptor availability (Bmax/Kd) at baseline conditions and after intravenous administration of either cocaine or methylphenidate. Cocaine (1-2 mg/kg) or methylphenidate (0.5 mg/kg) administered 5 min prior to [11C]raclopride decreased Bmax/Kd by 29+/-3% and 32 + 4%, respectively. Smaller reductions in Bmax/Kd (13% for cocaine given 30 min before [11C]raclopride and 25+/-10% for methylphenidate given 40 min before [11C]raclopride) were seen with longer periods between drug and radioligand. These observations are consistent with the slower striatal clearance kinetics of [11C]methylphenidate than [1C]cocaine observed in previous PET experiments and with the approximately twofold higher potency of methylphenidate than cocaine in in vitro experiments. Though the elevation of synaptic DA induced by >70% occupancy of DAT by these drugs lead to a modest increase in occupancy of D2 receptors (25-30%), further studies are required to assess if this is an underestimation because of differences in D2 receptor binding kinetics between raclopride and DA.

The aim of this study was to evaluate the prognostic value of pretreatment F-fluorodeoxyglucose PET/computed tomography (CT), particularly in the assessment of metabolic tumor burden markers such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG), with respect to clinical outcomes in stage I non-small-cell lung cancer (NSCLC) patients undergoing stereotactic body radiation therapy (SBRT).This retrospective study evaluated 50 patients who underwent SBRT for stage I NSCLC from May 2007 to December 2012. The maximum standardized uptake value (SUVmax), average SUV (SUVavg), MTV, and TLG were measured from the PET/CT scan. The study population was dichotomized at the median into high and low groups. Kaplan-Meier log-rank tests were then used to compare high with low PET/CT parameter groups, and univariate Cox proportional hazards regression analysis was carried out to identify predictors of overall survival.The 2-year local control rate was 93.7%. After a median follow-up of 25.1 months, the 2-year overall survival was 79.3%. Eight patients (16%) had disease recurrence. There were three local failures (6%), three mediastinal failures (6%), and six cases of distant metastases (12%). Both Kaplan-Meier actuarial analysis and Cox proportional hazards regression found no correlation between SUVmax, SUVavg, MTV, and TLG and overall survival.Standard PET/CT measures, such as SUVmax, as well as newer measures of metabolic tumor burden, such as MTV and TLG, were not correlated with overall survival in our study population of stage I NSCLC patients undergoing SBRT. Larger studies with longer follow-up periods are needed to confirm these results.

The effect on chronic crack users of a 3 month detoxification programme on lung clearance of inhaled 99 Tc m -diethylenetriamine pentaacetate ( 99 Tc m -DTPA) aerosol, spirometry and gas exchange was determined in a controlled in-patient clinical treatment setting. Imaging studies were carried out in eight chronic crack users (four crack-only and four crack plus tobacco) before and after the successful completion of the detoxification programme to measure the clearance of inhaled 99 Tc m -DTPA from the lungs, an index of lung epithelial permeability. 99 Tcm-DTPA lung clearance, expressed in terms of the biological half-time, T μ was determined from the slopes of the least-squares fit regression lines of the respective time-activity plots. The mean (± S.D.) global T 1/2 values of the crack-only (75±39 min) and crack plus tobacco users (22±10 min) were significantly shorter (P < 0.02 and P < 0.001, respectively) than from the lungs of the non-smoking controls (124±29 min). This was consistent with increased lung epithelial permeability secondary to crack-related lung injury. The mean global T 1/2 value of the crack plus tobacco users was significantly shorter (P

A 57-year-old-male presented for whole-body PET with CT for restaging of lung cancer. Besides revealing postradiation changes, we noticed an unusual pattern of FDG uptake in the myocardium, with prominent metabolic uptake involving 4 chambers of the heart. Later that day, the patient was referred to the emergency department for increased heart rate, but otherwise asymptomatic. CT angiography was performed, which showed scattered filling defects in bilateral pulmonary arteries consistent with pulmonary embolism. The finding of prominent FDG uptake involving all cardiac chambers in this patient is likely related to heart strain caused by acute pulmonary embolism.

A study was conducted to evaluate the feasibility of simultaneous dual radionuclide brainimaging with 123I and 99m Tc using photopeak image subtraction techniques or offset photopeak image acquisition. The contribution of the photons from one radionuclide to a second radionuclide’s photopeak energy window (crosstalk) was evaluated for SPECT and planar imaging of a brain phantom containing 123I and 99m Tc for a range of activity levels and distribution properties approximating those in rCBF images of the adult human brain. Crosstalk was evaluated for 10% symmetrical energy windows centered on the 123I and 99m Tc photopeaks and for 10% energy windows asymmetrically placed to the left and right of the center of the respective photopeaks. Major observations include: (1) in the centered photopeak windows, 99m Tc crosstalk in the 123I window is 8.9% of the 99m Tc seen in the 99m Tc window and ranges from 37.5% to 75.0% of the 123I in the 123I window. 123I crosstalk is 37.8% of the 123I seen in the 123I window and ranges from 4.4% to 8.9% of the 99m Tc seen in the 99m Tc window; (2) the spatial distribution of a radionuclide’s crosstalk photons differs from that observed in the radionuclide’s photopeak window; (3) a 99m Tc photopeak window offset to the left does not decrease 123I crosstalk, and the percentage of 99m Tc scatteredphotons is significantly increased in the window. Offsetting the 123I window to the right decreases 99m Tc crosstalk to 9.0% to 17.9% of the 123I counts, but decreases 123I sensitivity by 39.9%; and (4) offsetting both photopeak windows to the right decreases the 99m Tc scatteredphotons in the 99m Tc window, but increases 123I crosstalk to 17.0% to 33.8% of the 99m Tc counts. The findings show that image quality, spatial resolution, and quantitative accuracy are degraded to unacceptable levels with the combinations of energy windows tested for dual radionuclide imaging of 99m Tc and 123I. This indicates that dual radionuclide imaging must be thoroughly tested and validated before use in clinical studies.