A Pilot Study of Neurobiological Mechanisms of Stress and Cardiovascular Risk.

Objective: Coronary heart disease is a leading cause of death and disability. Although psychological stress has been identified as an important potential contributor, mechanisms by which stress increases risk of heart disease and mortality are not fully understood. The purpose of this study was to assess mechanisms by which stress acts through the brain and heart to confer increased CHD risk. Methods: Coronary Heart Disease patients (N=10) underwent cardiac imaging with [Tc-99m] sestamibi single photon emission tomography at rest and during a public speaking mental stress task. Patients returned for a second day and underwent positron emission tomography imaging of the brain, heart, bone marrow, aorta (indicating inflammation) and subcutaneous adipose tissue, after injection of [18F]2-fluoro-2-deoxyglucose for assessment of glucose uptake followed mental stress. Patients with (N=4) and without (N=6) mental stress-induced myocardial ischemia were compared for glucose uptake in brain, heart, adipose tissue and aorta with mental stress. Results: Patients with mental stress-induced ischemia showed a pattern of increased uptake in the heart, medial prefrontal cortex, and adipose tissue with stress. In the heart disease group as a whole, activity increase with stress in the medial prefrontal brain and amygdala correlated with stress-induced increases in spleen (r=0.69, p=0.038; and r=0.69, p=0.04 respectfully). Stress-induced frontal lobe increased uptake correlated with stress-induced aorta uptake (r=0.71, p=0.016). Activity in insula and medial prefrontal cortex was correlated with post-stress activity in bone marrow and adipose tissue. Activity in other brain areas not implicated in stress did not show similar correlations. Increases in medial prefrontal activity with stress correlated with increased cardiac glucose uptake with stress, suggestive of myocardial ischemia (r=0.85, p=0.004). Conclusions: These findings suggest a link between brain response to stress in key areas mediating emotion and peripheral organs involved in inflammation and hematopoietic activity, as well as myocardial ischemia, in Coronary Heart Disease patients.

Case report of lymph node activation mimicking cancer progression: A false positive F18 FDG PET CT after COVID-19 vaccination.

This case illustrates a false positive F18 FDG PET CT in the left axilla of a woman being treated for metastatic breast cancer after COVID-19 vaccination. Follow-up ultrasound of the axilla indicated no metastasis, indicating that the lymphadenopathy was likely due to an immune response following vaccination. This case report, in conjunction with prior studies of other vaccines with similar findings suggest that providers should be aware of potential false positive imaging following COVID-19 vaccination. In light of these findings, clinicians and imaging providers should record the date and side of the vaccination and inform patient of potential false positive results to reduce patient anxiety and unnecessary tests as COVID-19 vaccines become widely available.

Can the Diagnostic Accuracy of Bone Scintigraphy Be Maintained with Half the Scanning Time?

We aimed to show that the acquisition time of a conventional bone scan could be reduced by half without losing the diagnostic value of the scan. Methods: Fifty adult patients (37 male and 13 female; mean age, 62.5 y; SD, 8.7 y) were enrolled. The patients were injected with 925-1,110 MBq (25-30 mCi) of 99mTc-methylene diphosphonate intravenously. The standard-protocol whole-body planar images were acquired first (scan speed, 10 cm/min; acquisition time, ∼20 min) and were followed immediately by the half-time protocol whole-body planar images (scan speed, 20 cm/min; acquisition time, ∼10 min). Both sets of images were interpreted by 2 nuclear medicine physicians. Each reviewer, when reviewing the standard-protocol images, was self-masked to the result he or she had obtained when reviewing the half-time images, and vice versa. This self-masking was accomplished by allowing a minimum of 2 wk to elapse between the 2 interpretations. We used the κ-coefficient to compare agreement between the standard-protocol results and the half-time results. Results: There was no difference in clinically significant diagnostic information between the half-time and standard protocols. The diagnostic quality of half-time and standard-protocol images did not significantly differ (0.86 < κ < 1.0). Conclusion: Our data suggest that if we reduce the 99mTc-methylene diphosphonate dose by half and keep the acquisition time at its standard value, we gain the benefit of reduced dose without loss of diagnostic value.

PET and SPECT Imaging of Epilepsy: Technical Considerations, Pathologies, and Pitfalls.

Epilepsy is generated by a plethora of varying pathologies, structural lesions, and pathways and may significantly impact a patient's livelihood. The combination of clinical semiology, electroencephalogram, and magnetic resonance imaging often fails to identify a structural seizure focus. The addition of functional radionuclide imaging is complementary to structural imaging and essential when structural imaging is discordant or inconclusive. The understanding of the key radiopharmaceuticals, imaging techniques, spectrum of disease processes, and potential pitfalls is necessary for diagnosis and surgical planning in epilepsy.

Sentinel-Lymph-Node Multicenter Trials.

Well executed multicenter clinical trials often provide significant evidence and support for, or against, foundational aspects of clinical procedures perceived to improve clinical management of a medical condition. In this review, discussed are reports of multicenter clinical trials designed to investigate sentinel lymph node biopsy procedures in seven types of cancer: breast, melanoma, head and neck, gastric, colon, uterine, and vulvar-with focus on the most recent reports of the hypotheses, objectives, parameters, data, results, implications, and impacts of the included trials. Such trials generally enroll more subjects, in shorter time periods, than do single-center studies. Such studies generally also have greater diversities among investigator practitioners and investigative environments than do single-center studies. The greater number of subjects provides more power to statistical analyses performed in such studies. The more rapid accrual usually results in data being more consistently acquired. The diversities of practitioners and environments may produce results that are more conservative than might be obtained from more "focused" studies; however, diversities in a study often identify implicitly results that are more robust-that is results applicable by more practitioners and applicable in more environments.

Development and validation of an automatic method to detect the latest contracting viable left ventricular segments to assist guide CRT therapy from gated SPECT myocardial perfusion imaging.

OBJECTIVES: The purpose of this study is to use ECG-gated SPECT MPI to detect the latest contracting viable left ventricular (LV) segments to help guide the LV probe placement used in CRT therapy and to validate segment selection against the visual integration method by experts. METHODS: For each patient, the resting ECG-gated SPECT MPI short-axis images were sampled in 3D to generate a polar map of the perfusion distribution used to determine LV myocardial viability, and to measure LV synchronicity using our phase analysis tool. In the visual integration method, two experts visually interpreted the LV viability and mechanical dyssynchrony from the short-axis images and polar maps of viability and phase, to determine the latest contracting viable segments using the 17-segment model. In the automatic method, the apical segments, septal segments, and segments with more than 50% scar were excluded as these are not candidates for CRT LV probe placement. Amongst the remaining viable segments, the segments, whose phase angles were within 10° of the latest phase angle (the most delayed contracting segment), were identified for potential CRT LV probe placement and ranked based on the phase angles of the segments. Both methods were tested in 36 pre-CRT patients who underwent ECG-gated SPECT MPI. The accuracy was determined as the percent agreement between the visual integration and automatic methods. The automatic method was performed by a second independent operator to evaluate the inter-operator processing reproducibility. RESULTS: In all the 36 patients, the LV lead positions of the 1st choices recommended by the automatic and visual integration methods were in the same segments in 35 patients, which achieved an agreement rate of 97.2%. In the inter-operator reproducibility test, the LV lead positions of the 1st choices recommended by the two operators were in the same segments in 25 patients, and were in the adjacent segments in 7 patients, which achieved an overall agreement of 88.8%. CONCLUSIONS: An automatic method has been developed to detect the latest contracting viable LV segments to help guide the LV probe placement used in CRT therapy. The retrospective clinical study with 36 patients suggests that this method has high agreement against the visual integration method by experts and good inter-operator reproducibility. Consequently, this method is promising to be a clinical tool to recommend the CRT LV lead positions.

Sentinel Lymph Node Biopsy Procedures.

Accurate staging of many cancers with no clinical evidence of lymph node involvement is often a critical component of the management of such cancers and is generally and historically accomplished by accurate pathological assessment of multiple nodes. Unfortunately, such assessment usually involves excision of the multiple nodes and can result in significant morbidities. Over the past half century, and particularly over the last quarter century, investigators have defined and refined the "sentinel lymph node(s)" concept and have developed and investigated sentinel lymph node biopsy (SLNB) procedures. Such procedures are designed to stage cancers primarily via assessment of the sentinel nodes of the cancers and to do so with limited risk of morbidities. For some cancers (e.g., breast, melanoma, head and neck, penile), there are SLNB procedures that are used routinely. For other cancers, there are SLNB procedures being investigated that will yet prove successful and practical or successful but not practical or neither practical nor successful. In this review, SLNB procedures for breast, melanoma (adult and pediatric), head-and-neck, gastrointestinal (gastric, esophageal, colon), genitourinary (penile, prostate), and gynecological (uterine, cervical, vulvar, ovarian) cancers are discussed, including results of significant clinical trials performed using such in the management of these various cancers.

Multimodality Radionuclide Imaging in a Patient With Hereditary Paraganglioma-Pheochromocytoma Syndrome.

Hereditary paraganglioma (PGL)-pheochromocytoma (PCC) syndrome is a genetic disorder caused by a mutation of the tumor suppressor gene SDHD that results in a predisposition for head and neck PGLs and PCCs. We present a case of a 33-year-old woman where F-FDG PET/CT showed areas of increased uptake in both the adrenal and cervical regions, consistent with PCCs and PGLs, respectively. Further imaging revealed that PCCs were I-MIBG avid, whereas the PGLs were In-octreotide avid. This demonstrates the varying sensitivities of different imaging modalities in regard to neuroendocrine tumors and the potential for treatment using multiple targeted therapies.

Utility of gray-matter segmentation of ictal-Interictal perfusion SPECT and interictal 18F-FDG-PET in medically refractory epilepsy.

PURPOSE: We present a method of gray-matter segmentation of functional neuroimaging for localization of seizure onset zone (SOZ) in epilepsy surgery. 18F-FDG-PET hypometabolism and ictal SPECT hyperperfusion may correspond to SOZ. We hypothesize that limiting functional images to gray matter improves identification of small, subtle, or obscure cortical volumes of 18F-FDG-PET hypometabolism and eliminates hyperperfused seizure propagation pathways within white matter in ictal perfusion SPECT. METHODS: Twenty-five adult and pediatric patients age 2-48 years with epilepsy surgery evaluations consisting of MRI, 18F-FDG-PET, ictal and interictal perfusion SPECT, and intracranial EEG (iEEG) monitoring were selected. MRI gray matter segmentation was used to identify cortical regions in coregistered 18F-FDG-PET and Ictal-Interictal SPECT Analysis by SPM (ISAS) as volumes of interest (VOI). VOIs in 18F-FDG-PET and SPECT perfusion clusters were compared to iEEG localization. The level of VOI concordance between two modalities was recorded as the same subgyrus (highest concordance), gyrus, sublobe, lobe, hemisphere, or no concordance. RESULTS: With segmentation, 84% (21/25) of cases had at least one area identified on 18F-FDG-PET scan concordant with iEEG SOZ at sublobar or higher levels, and 72% (18/25) of cases had subgyral concordance with iEEG SOZ. Without segmentation, 60% (15/25) of cases had at least one area in 18F-FDG-PET scan concordant with iEEG SOZ at sublobar or higher levels, and 32% (8/25) with subgyral concordance. 83% (10/12) of seizure free patients had subgyral concordance on segmented 18F-FDG-PET. Both segmented and nonsegmented ictal-interictal SPECT perfusion clusters had 56% (14/25) of cases with at least sublobar concordance. Subgyral concordance was achieved by 28% (7/25) of segmented and 20% (5/25) of nonsegmented SPECTs. DISCUSSION: Segmented 18F-FDG-PET scans frequently result in high correspondence to iEEG onset zones with localizations exactly concordant with iEEG SOZ- more than twice as often as without segmentation. Segmentation allows for the identification of small or subtle areas of hypometabolism that are often unappreciated or are obscured by normally hypometabolic white matter. Segmentation of ictal-interictal SPECT clusters did not significantly increase localization with iEEG SOZ over nonsegmented clusters.

Radionuclide Therapies in Molecular Imaging and Precision Medicine.

This article reviews recent advances and applications of radionuclide therapy. Individualized precision medicine, new treatments, and the evolving role of radionuclide therapy are discussed.

Lymphoscintigraphy and sentinel nodes.

It has been validated that sentinel lymph node biopsy (SLNB) shows whether a patient's breast cancer or melanoma has spread to regional lymph nodes. As a result, management of patients with these cancers has been revolutionized. SLNB has replaced axillary lymph node dissection (ALND) as the staging modality of choice for early breast cancer and has replaced complete lymph node dissection as the staging modality of choice for melanoma in patients whose SLNBs indicate no metastases. Recently concluded multicenter, randomized trials for breast cancer with 5- to 10-y outcome data have shown no significant differences in disease-free survival rates or overall survival rates between SLNB and ALND groups but have shown significantly lower morbidity with SLNB than with ALND. The lowest false-negative rates (5.5%-6.7%) were seen in studies that used preoperative lymphoscintigraphy and dual mapping during surgery. To assess the survival impact of SLNB in melanoma, the Multicenter Selective Lymphadenectomy Trial I was performed. Melanoma-specific survival rates were not different between subjects randomized to SLNB with lymphadenectomy for nodal metastasis on biopsy and subjects randomized to observation with lymphadenectomy for nodal relapse. However, the 10-y disease-free survival rates were better for the SLNB group than for the observation group, specifically among patients with intermediate-thickness melanomas or thick melanomas.

Sodium 18F-Fluoride Bone Scintigraphy in Deep Ocean Diver.

Sodium ¹8F-fluoride (NaF) is a diagnostic marker for new bone formation in bone scintigraphy that was approved by US FDA in 1972 but discontinued in 1984. We report a case of a US naval officer who spent time living and working in an oceanic lab, 205 feet below the surface. Plain skeletal films of femurs 4 years later demonstrate bilateral bone infarcts. Corresponding sodium ¹8F-fluoride bone scintigraphy demonstrates low-normal to decreased tracer activity. This rectilinear scan image is of historical interest. Other bone scintigraphic radiotracers used in the past and present will be briefly discussed.

The nuclear medicine therapy care coordination service: a model for radiologist-driven patient-centered care.

We developed a longitudinal care coordination service to proactively deliver high-quality and family-centered care in patients receiving radioiodine therapy for thyroid cancer. In an iterative, multidisciplinary team manner, a pretherapy consultation service, which included scripted interactions, documentation, and checklists for quality control, evolved over time into a robust patient-centered longitudinal care coordination nuclear medicine service. Radiation safety precautions, the rationale for therapy, and management of patient expectations were addressed through the initial consultation, and discharge and posttreatment care were managed during subsequent follow-up. The patient-physician relationship created during longitudinal nuclear medicine therapy care is one tool to help counteract the growing commoditization of radiology. This article describes the process that the nuclear medicine specialists in our department established to enhance radiologist value by providing both exceptional thyroid cancer treatment and continuity of care.

Nuclear medicine imaging and therapy: gender biases in disease.

Gender-based medicine is medical research and care conducted with conscious consideration of the sex and gender differences of subjects and patients. This issue of Seminars is focused on diseases for which nuclear medicine is part of routine management and for which the diseases have sex- or gender-based differences that affect incidence or pathophysiology and that thus have differences that can potentially affect the results of the relevant nuclear medicine studies. In this first article, we discuss neurologic diseases, certain gastrointestinal conditions, and thyroid conditions. The discussion is in the context of those sex- or gender-based aspects of these diseases that should be considered in the performance, interpretation, and reporting of the relevant nuclear medicine studies. Cardiovascular diseases, gynecologic diseases, bone conditions such as osteoporosis, pediatric occurrences of some diseases, human immunodeficiency virus-related conditions, and the radiation dose considerations of nuclear medicine studies are discussed in the other articles in this issue.

The EANM and SNMMI practice guideline for lymphoscintigraphy and sentinel node localization in breast cancer.

PURPOSE: The accurate harvesting of a sentinel node in breast cancer includes a sequence of procedures with components from different medical specialities, including nuclear medicine, radiology, surgical oncology and pathology. The aim of this document is to provide general information about sentinel lymph node detection in breast cancer patients. METHODS: The Society of Nuclear Medicine and Molecular Imaging (SNMMI) and the European Association of Nuclear Medicine (EANM) have written and approved these guidelines to promote the use of nuclear medicine procedures with high quality. The final result has been discussed by distinguished experts from the EANM Oncology Committee, the SNMMI and the European Society of Surgical Oncology (ESSO). CONCLUSION: The present guidelines for nuclear medicine practitioners offer assistance in optimizing the diagnostic information from the SLN procedure. These guidelines describe protocols currently used routinely, but do not include all existing procedures. They should therefore not be taken as exclusive of other nuclear medicine modalities that can be used to obtain comparable results. It is important to remember that the resources and facilities available for patient care may vary.

Status of sentinel lymph node for breast cancer.

Long-awaited results from randomized clinical trials designed to test the validity of sentinel lymph node biopsy (SLNB) as replacement of axillary lymph node dissection (ALND) in management of early breast cancer have recently been published. All the trials conclude SLNB has survival rates comparable to those of ALND (up to 10 years in one study) and conclude SLNB has less morbidity than ALND. All the trials support replacing ALND with SLNB for staging in early breast cancer; all support SLNB as the standard of care for such cancer. The SLNB protocols used in the trials varied, and no consensus that would suggest a standard protocol exists. The results of the trials and of other peer-reviewed research do, however, suggest a framework for including some specific methodologies in accepted practice. This article highlights the overall survival and disease-free survival data as reported from the clinical trials. This article also reviews the status of SLN procedures and the following: male breast cancer, the roles of various imaging modalities (single-photon emission computed tomography/computed tomography, positron emission tomography/computed tomography, and ultrasound), ductal carcinoma in situ, extra-axillary SLNs, SLNB after neoadjuvant chemotherapy, radiation exposure to patients and medical personnel, and a new radiotracer that is the first to label SLNs not by particle trapping but by specific macrophage receptor binding. The proper Current Procedural Terminology (CPT) code for lymphoscintigraphy and SLN localization prior to surgery is 78195.

Recombinant human bone morphogenetic protein 2-induced heterotopic ossification of the retroperitoneum, psoas muscle, pelvis and abdominal wall following lumbar spinal fusion.

A 45-year-old man presented with vertebral collapse at L5 as an initial manifestation of multiple myeloma and underwent spinal fusion surgery using recombinant human bone morphogenetic protein-2 (rhBMP-2). Subsequent computed tomography (CT) scans and X-rays revealed heterotopic ossification of the left psoas muscle, pelvis, and anterior abdominal wall. While the occurrence of heterotopic ossification has previously been reported when rhBMP-2 has been used for spinal fusion surgery, this case demonstrates that it can occur to a much greater degree than previously seen.