Myocardial perfusion imaging-derived left ventricular strain: Regional abnormalities associated with transthyretin cardiac amyloidosis.

Background: Transthyretin (ATTR) cardiac amyloidosis is associated with an apical-sparing strain pattern on TTE. We hypothesize that strain indices derived from myocardial perfusion imaging (MPI) can identify this abnormality. Methods: A group with ATTR amyloidosis was compared to age-matched controls with LVH but without amyloidosis who underwent PET or SPECT MPI. Strain values were used to calculate the apical strain index (ASI), apex-to-base ratio (ABR), and ejection fraction to global strain ratio in multiple planes. Results: A direct comparison using Welch's t-tests reveals 6 statistically significant metrics. After regression analysis, the circumferential ASI and ABR at rest remain significantly greater in the ATTR group compared to controls. Conclusion: MPI-derived strain from the circumferential plane at rest may distinguish cardiac amyloidosis from other forms of LVH. If these findings are confirmed with validation studies, routine MPI-derived strain analysis could identify patients with subclinical amyloidosis who may benefit from further testing.

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.

Computer assisted interpretation of Tc-99m mercaptoacetyltriglycine diuretic scintigraphy enhances resident performance.

OBJECTIVE: iRENEX is a software module that incorporates scintigraphic and clinical data to interpret 99m Tc- mercaptoacetyltriglycine (MAG3) diuretic studies and provide reasons for their conclusions. Our objectives were to compare iRENEX interpretations with those of expert physicians, use iRENEX to evaluate resident performance and determine if iRENEX could improve the diagnostic accuracy of experienced residents. METHODS: Baseline and furosemide 99m Tc-MAG3 acquisitions of 50 patients with suspected obstruction (mean age ± SD, 58.7 ±â€…15.8 years, 60% female) were randomly selected from an archived database and independently interpreted by iRENEX, three expert readers and four nuclear medicine residents with one full year of residency. All raters had access to scintigraphic data and a text file containing clinical information and scored each kidney on a scale from +1.0 to -1.0. Scores ≥0.20 represented obstruction with higher scores indicating greater confidence. Scores +0.19 to -0.19 were indeterminate; scores ≤-0.20 indicated no obstruction. Several months later, residents reinterpreted the studies with access to iRENEX. Receiver operating characteristic (ROC) analysis and concordance correlation coefficient (CCC) quantified agreement. RESULTS: The CCC among experts was higher than that among residents, 0.84, versus 0.39, respectively, P  < 0.001. When residents reinterpreted the studies with iRENEX, their CCC improved from 0.39 to 0.73, P  < 0.001. ROC analysis showed significant improvement in the ability of residents to distinguish between obstructed and non-obstructed kidneys using iRENEX ( P  = 0.036). CONCLUSION: iRENEX interpretations were comparable to those of experts. iRENEX reduced interobserver variability among experienced residents and led to better agreement between resident and expert interpretations.

Obstructive sleep apnea, myocardial perfusion and myocardial blood flow: A study of older male twins.

BACKGROUND: Obstructive sleep apnea (OSA) has been associated with incidence of cardiovascular disease and with nocturnal angina, but evidence of a link with coronary atherosclerosis and myocardial ischemia is limited and previous studies may have been affected by selection bias or unmeasured confounding factors. METHODS: We performed overnight polysomnography in 178 older male twins. The Apnea/Hypopnea Index (AHI) was calculated to assess OSA from the overnight sleep evaluation. AHI ≥15 was used as indicator of moderate/severe OSA. The following day, twins underwent myocardial perfusion imaging with [82Rb]-chloride positron emission tomography. Quantitative and semiquantitative measures of myocardial perfusion and absolute myocardial blood flow were obtained. RESULTS: The mean age was 68 years and 40% of the sample had an AHI≥15, which indicates moderate to severe OSA. Abnormal myocardial perfusion, both with stress and at rest, was more common in twins with elevated AHI. After adjusting for clinical, lifestyle and behavioral factors, and previous history of cardiovascular disease, twins with AHI ≥15 had 3.6 higher odds (95% CI, 1.5-8.9) of an abnormal total severity score, defined as a score ≥100, and for each 5-point increment in AHI, the odds of abnormality increased by 20% (95% CI, 7%-34%). Twin pairs where both twins had OSA exhibited the greatest risk. There were no differences in measures of ischemia and absolute myocardial blood flow and flow reserve by AHI status. CONCLUSIONS: OSA is associated with myocardial perfusion abnormalities that suggest prior subclinical myocardial scarring or infarction. Early environmental factors that affect both twins equally may play a role and should be further explored.

Risk Factors Associated With New-Onset Myocardial Perfusion Abnormalities in Kidney Transplant Candidates.

The optimal coronary artery disease surveillance strategy for end-stage renal disease patients being evaluated for kidney transplantation is unknown. It is unclear what risk factors are associated with the development of new-onset perfusion abnormalities on serial myocardial perfusion imaging. Potential kidney transplant recipients who underwent 2 myocardial perfusion imaging studies at Emory University Hospital between January 2010 and December 2019 were identified. We assessed the frequency of development of any new perfusion defect and development of moderate to severe ischemia (reversible perfusion defect >10%) on serial imaging. Finally, we identified the clinical and imaging factors associated with new perfusion defects and explored the association between new perfusion defects and all-cause mortality. History of myocardial infarction (MI) and peripheral artery disease was associated with an increased risk of developing a new perfusion defect. History of MI was also associated with the risk of developing moderate-severe ischemia. Female patients were less likely to develop new perfusion defects or moderate-severe ischemia. There was no association between either outcome and all-cause mortality. In conclusion, a history of MI, peripheral artery disease, and male gender are risk factors for developing new perfusion defects, although only the history of MI and male gender predict moderate to severe ischemia. Interval development of any abnormal perfusion is not associated with increased mortality.

Posttraumatic Stress Disorder, Myocardial Perfusion, and Myocardial Blood Flow: A Longitudinal Twin Study.

BACKGROUND: The link between posttraumatic stress disorder (PTSD) and ischemic heart disease remains elusive owing to a shortage of longitudinal studies with a clinical diagnosis of PTSD and objective measures of cardiac compromise. METHODS: We performed positron emission tomography in 275 twins who participated in two examinations approximately 12 years apart. At both visits, we obtained a clinical diagnosis of PTSD, which was classified as long-standing (both visit 1 and visit 2), late onset (only visit 2), and no PTSD (no PTSD at both visits). With positron emission tomography, we assessed myocardial flow reserve (MFR), which, in absence of significant coronary stenoses, indexes coronary microvascular function. We compared positron emission tomography data at visit 2 across the three categories of longitudinally assessed PTSD and examined changes between the two visits. RESULTS: Overall, 80% of the twins had no or minimal obstructive coronary disease. Yet, MFR was depressed in twins with PTSD and was progressively lower across groups with no PTSD (2.13), late-onset PTSD (1.97), and long-standing PTSD (1.93) (p = .01). A low MFR (a ratio <2.0) was present in 40% of the twins without PTSD, in 56% of those with late-onset PTSD, and in 72% of those with long-standing PTSD (p < .001). Associations persisted in multivariable analysis, when examining changes in MFR between visit 1 and visit 2, and within twin pairs. Results were similar by zygosity. CONCLUSIONS: Longitudinally, PTSD is associated with reduced coronary microcirculatory function and greater deterioration over time. The association is especially noted among twins with chronic, long-standing PTSD and is not confounded by shared environmental or genetic factors.

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.

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.

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.

Diagnostic performance of an artificial intelligence-driven cardiac-structured reporting system for myocardial perfusion SPECT imaging.

OBJECTIVES: To describe and validate an artificial intelligence (AI)-driven structured reporting system by direct comparison of automatically generated reports to results from actual clinical reports generated by nuclear cardiology experts. BACKGROUND: Quantitative parameters extracted from myocardial perfusion imaging (MPI) studies are used by our AI reporting system to generate automatically a guideline-compliant structured report (sR). METHOD: A new nonparametric approach generates distribution functions of rest and stress, perfusion, and thickening, for each of 17 left ventricle segments that are then transformed to certainty factors (CFs) that a segment is hypoperfused, ischemic. These CFs are then input to our set of heuristic rules used to reach diagnostic findings and impressions propagated into a sR referred as an AI-driven structured report (AIsR). The diagnostic accuracy of the AIsR for detecting coronary artery disease (CAD) and ischemia was tested in 1,000 patients who had undergone rest/stress SPECT MPI. RESULTS: At the high-specificity (SP) level, in a subset of 100 patients, there were no statistical differences in the agreements between the AIsr, and nine experts' impressions of CAD (P = .33) or ischemia (P = .37). This high-SP level also yielded the highest accuracy across global and regional results in the 1,000 patients. These accuracies were statistically significantly better than the other two levels [sensitivity (SN)/SP tradeoff, high SN] across all comparisons. CONCLUSIONS: This AI reporting system automatically generates a structured natural language report with a diagnostic performance comparable to those of experts.

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.

(90)Y Radioembolization: Multimodality Imaging Pattern Approach with Angiographic Correlation for Optimized Target Therapy Delivery.

Primary and metastatic liver cancers are responsible for considerable morbidity and mortality, and many patients are not curable at presentation. Therefore, new therapies such as radioembolization with yttrium 90 ((90)Y)-labeled microspheres are an alternative method to treat patients with unresectable primary or secondary liver tumors. Patient selection, treatment technique, and early recognition of potential complications are the keys for successful patient outcomes. The activity of administered (90)Y microspheres depends on multiple variables, including the tumor burden, the volume of the liver lobe to be treated, the type of (90)Y microspheres, and the hepatopulmonary shunt fraction. Preprocedural planning relies on the results of cross-sectional imaging to determine the extent of disease, tumoral and nontumoral liver volumes, patency of the portal vein, and the degree of extrahepatic disease. A multidisciplinary approach that combines expertise in cross-sectional imaging, nuclear medicine, and flow dynamics is critical to adequately target malignant tissue. Preprocedural multimodality imaging, particularly combined single photon emission computed tomography (SPECT) and computed tomography (CT) imaging (SPECT/CT), may be used to identify nontarget imaging patterns that, if recognized, can potentially be corrected with either branch vessel embolization or catheter repositioning. Postprocedural multimodality imaging is also useful to confirm the appropriate delivery of (90)Y microspheres, enabling early identification of potential complications and the adequacy of microsphere distribution, thereby optimizing planning for subsequent therapies.