Contemporary Cardiac SPECT Imaging-Innovations and Best Practices: An Information Statement from the American Society of Nuclear Cardiology.

This information statement from the American Society of Nuclear Cardiology highlights advances in cardiac SPECT imaging and supports the incorporation of new technology and techniques in laboratories performing nuclear cardiology procedures. The document focuses on the application of the latest imaging protocols and the utilization of newer hardware and software options to perform high quality, state-of-the-art SPECT nuclear cardiology procedures. Recommendations for best practices of cardiac SPECT imaging are discussed, highlighting what imaging laboratories should be doing as the standard of care in 2018 to achieve optimal results (based on the ASNC 2018 SPECT guideline [Dorbala et al., J Nucl Cardiol. 2018. https://doi.org/10.1007/s12350-018-1283-y ]).

Is There a Role for PET/CT Parameters to Characterize Benign, Malignant, and Metastatic Parotid Tumors?

OBJECTIVE: Assessment of benign and malignant lesions of the parotid gland, including metastatic lesions, is challenging with current imaging methods. Fluorine-18 FDG PET/CT is a noninvasive imaging modality that provides both anatomic and metabolic information. Semiquantitative data obtained from PET/CT, also known as PET/CT parameters, are maximum, mean, or peak standardized uptake values (SUVs); metabolic tumor volume; total lesion glycolysis; standardized added metabolic activity; and normalized standardized added metabolic activity. Our aim was to determine whether FDG PET/CT parameters can differentiate benign, malignant, and metastatic parotid tumors. MATERIALS AND METHODS: Thirty-four patients with parotid neoplasms underwent PET/CT before parotidectomy; maximum SUV, mean SUV, peak SUV, total lesion glycolysis, metabolic tumor volume, standardized added metabolic activity, and normalized standardized added metabolic activity were calculated on a dedicated workstation. Univariate analyses were performed. A ROC analysis was used to determine the ability of PET/CT parameters to predict pathologically proven benign, malignant, and metastatic parotid gland neoplasms. RESULTS: Fourteen patients had a benign or malignant primary parotid tumor. Twenty had metastases to the parotid gland. When the specificity was set to at least 85% for each parameter to identify cut points, the corresponding sensitivities ranged from 15% to 40%. Assessment of benign versus malignant lesions of parotid tumors, as well as metastasis from squamous cell carcinoma versus other metastatic causes, revealed that none of the PET/CT parameters has enough power to differentiate among these groups. CONCLUSION: PET/CT parameters, including total lesion glycolysis, metabolic tumor volume, standardized added metabolic activity, and normalized standardized added metabolic activity, are not able to differentiate benign from malignant parotid tumors, primary parotid tumors from metastasis, or metastasis from squamous cell carcinoma and nonsquamous cell carcinoma metastasis.

(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.

Quantitative dosimetry for yttrium-90 radionuclide therapy: tumor dose predicts fluorodeoxyglucose positron emission tomography response in hepatic metastatic melanoma.

PURPOSE: To assess a new method for generating patient-specific volumetric dose calculations and analyze the relationship between tumor dose and positron emission tomography (PET) response after radioembolization of hepatic melanoma metastases. METHODS AND MATERIALS: Yttrium-90 ((90)Y) bremsstrahlung single photon emission computed tomography (SPECT)/computed tomography (CT) acquired after (90)Y radioembolization was convolved with published (90)Y Monte Carlo estimated dose deposition kernels to create a three-dimensional dose distribution. Dose-volume histograms were calculated for tumor volumes manually defined from magnetic resonance imaging or PET/CT imaging. Tumor response was assessed by absolute reduction in maximum standardized uptake value (SUV(max)) and total lesion glycolysis (TLG). RESULTS: Seven patients with 30 tumors treated with (90)Y for hepatic metastatic melanoma with available (90)Y SPECT/CT and PET/CT before and after treatment were identified for analysis. The median (range) for minimum, mean, and maximum dose per tumor volume was 16.9 Gy (5.7-43.5 Gy), 28.6 Gy (13.8-65.6 Gy) and 36.6 Gy (20-124 Gy), respectively. Response was assessed by fluorodeoxyglucose PET/CT at a median time after treatment of 2.8 months (range, 1.2-7.9 months). Mean tumor dose (P = .03) and the percentage of tumor volume receiving ≥ 50 Gy (P < .01) significantly predicted for decrease in tumor SUV(max), whereas maximum tumor dose predicted for decrease in tumor TLG (P < .01). CONCLUSIONS: Volumetric dose calculations showed a statistically significant association with metabolic tumor response. The significant dose-response relationship points to the clinical utility of patient-specific absorbed dose calculations for radionuclide therapy.

A simple method for estimating dose delivered to hepatocellular carcinoma after yttrium-90 glass-based radioembolization therapy: preliminary results of a proof of concept study.

PURPOSE: To investigate a simple semiquantitative method to estimate yttrium-90 ((90)Y) dose delivered with radioembolization to infiltrative hepatocellular carcinoma (HCC). MATERIALS AND METHODS: In a prospective study, patients with infiltrative HCC and portal vein thrombosis (PVT) underwent glass-based (90)Y radioembolization including technetium-99m macroaggregated albumin ((99m)Tc-MAA) hepatopulmonary shunt study before therapy and bremsstrahlung single photon emission computed tomography (SPECT)/computed tomography (CT) after (90)Y radioembolization. Baseline magnetic resonance imaging was coregistered with (99m)Tc-MAA and bremsstrahlung SPECT/CT imaging separately. Unit tumor activity ((90)Y radioactivity delivered to each cubic centimeter of tumor) was estimated based on a lobar infusion approach. Correlation between proportions of (99m)Tc-MAA and (90)Y delivered to the tumor was investigated. Survival analysis was performed using Kaplan-Meier estimations. RESULTS: (90)Y therapy was administered in 18 consecutive patients (median age, 55.3 y; mean tumor volume, 588 cm(3)). Higher intratumoral (90)Y dose predicted prolonged survival, with 13.2-month median survival in patients with HCC and mean (90)Y dose of ≥ 100 Gy versus 4.6-month median survival for other patients (P < .001). Of administered (90)Y dose, 51.9% was delivered to the targeted tumors compared with 74.1% of (99m)Tc-MAA with linear correlation between biodistribution of (99m)Tc-MAA and (90)Y observed (Pearson r = 0.774, P < .001). CONCLUSIONS: The findings in this study suggest that approximately 50% of administered (90)Y dose is taken up by targeted infiltrative HCC with PVT. Intratumoral (90)Y dose ≥ 100 Gy in unresectable infiltrative HCC via a lobar intraarterial approach is a positive prognostic factor for survival.

Diagnostic performance of low-dose rest/stress Tc-99m tetrofosmin myocardial perfusion SPECT using the 530c CZT camera: quantitative vs visual analysis.

BACKGROUND: We set out to develop normal databases and prospectively validate abnormality criteria for a low-dose Tc-99m tetrofosmin myocardial perfusion SPECT protocol using the 530c CZT camera. METHODS: All patients received 6 mCi rest/20 mCi stress doses of Tc-99m tetrofosmin. Rest and stress images were obtained over 7-9 and 5-7 minutes according to the chest size. Low-dose CT of the chest was obtained on a standalone CT scanner. Forty patients with very low likelihood (LLK) of coronary artery disease (CAD) were used to define the normal count distributions. The abnormality criteria were prospectively validated in 55 patients who had coronary angiography and in 40 patients with LLK of CAD. RESULTS: The results for quantitative non-attenuation-corrected (AC) and AC analysis and visual analysis were as follows: sensitivity of 79%, 85%, and 92% (P = NS) and specificity of 44%, 75%, and 56% (P = NS), respectively. The normalcy rates for quantitative non-AC and AC analyses and visual analysis were 95%, 98%, and 98% (P = NS). CONCLUSIONS: We have developed non-AC and AC normal databases for low-dose rest/stress Tc-99m tetrofosmin myocardial perfusion SPECT protocol using the 530c CZT camera. The per-patient diagnostic performance of quantitative analyses is not significantly different from visual analysis by an experienced reader.

Proximal and Distal Gastric Retention Patterns in Gastroparesis and the Impact of Gastric Per-Oral Endoscopic Myotomy: A Retrospective Analysis Using Gastric Emptying Scintigraphy.

Gastroparesis is a debilitating disease of insufficient gastric emptying and visceral hypersensitivity characterized by nausea, vomiting, early satiety, and bloating. Gastric emptying scintigraphy (GES), in combination with typical symptoms and normal esophagogastroduodenoscopy findings, is used to diagnose the disease. Gastric per-oral endoscopic pyloromyotomy (G-POEM) has emerged as a novel technique for treating gastroparesis, with up to an 80% success rate. This procedure involves myotomy of the distal stomach. We hypothesize that responders to this therapy are characterized by more distal dysmotility than nonresponders, as defined by GES retention patterns. Methods: We used regional gastric emptying measurements from diagnostic GES to determine the proximal or distal predominance of disease for each patient. We then compared treatment response and symptoms in each patient to total gastric half-emptying time (T½), proximal gastric T½, and a ratio comparing the 2 values. Results: In total, 47 patients underwent G-POEM during the study period. A significant difference (P < 0.01) was found in proximal-to-total T½ ratio between responders and nonresponders. A significant difference between pre- and postprocedural proximal-to-total T½ ratios was identified for each patient. No correlations were identified between motility patterns and symptoms or in motility patterns among the different etiologies of the disease. Conclusion: Proximal-to-total T½ ratio may represent an important patient selection factor for G-POEM versus other treatment modalities going forward. Local retention patterns in GES may not inform the symptom profile in gastroparesis.

SNMMI Procedure Standard/EANM Guideline for Gated Equilibrium Radionuclide Angiography.

The purpose of this document is to assist nuclear medicine practitioners in recommending, performing, interpreting, and reporting the results of gated equilibrium radionuclide angiocardiography (ERNA).

Incidence of Radioembolization-Induced Liver Disease and Liver Toxicity Following Repeat 90Y-Radioembolization: Outcomes at a Large Tertiary Care Center.

PURPOSE: The complication profile following repeat Y-radioembolization (RE) is not well understood, and repeat RE is sometimes avoided because of concerns for RE-induced liver disease (REILD) and liver toxicity. The purpose of this study was to examine the incidence of REILD and liver toxicity following repeat Y-RE and to identify potential risk factors. METHODS: A retrospective analysis of patients undergoing repeat RE to the same hepatic lobe between 2013 and 2018 was performed. Baseline factors were evaluated as predictors of liver toxicity, mortality, and REILD, which was defined as the presence symptomatic ascites or jaundice in the absence of biliary obstruction within 8 weeks following RE. Post-RE complications were graded according to the Common Terminology Criteria for Adverse Events version 5. RESULTS: A total of 39 patients underwent repeat RE with 14 (35.9%) experiencing Common Terminology Criteria for Adverse Events toxicity of grade 2 or greater, 3 (10.3%) grade 3, and no grade 4 or greater. A Model for End Stage Liver Disease score of 8 or greater was associated with grade 2 toxicity or greater (26.7% vs 75%; P = 0.013). Only 3 patients (7.7%) experienced REILD due to symptomatic ascites without jaundice. Greater than 2 REs were associated with a greater rate of 6-month mortality (12% vs 58.3%, P = 0.003), 12-month mortality (28% vs 75%, P = 0.007), and REILD (0% vs 21.4%, P = 0.016). Age, sex, microsphere type, cirrhosis, Child-Pugh, and Eastern Cooperative Oncology Group status were not significantly associated with complications, REILD, or survival. CONCLUSIONS: Repeat Y-RE appears to be well tolerated with a low rate of high-grade adverse events and REILD.

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.

Improved quantification in 123I cardiac SPECT imaging with deconvolution of septal penetration.

OBJECTIVES: (123)I is becoming an important radionuclide for cardiac imaging. Multiple, low-abundance, high-energy photons associated with (123)I imaging can cause septal penetration in the collimators and degrade quantification of the (123)I cardiac uptake. This study presents a method for the deconvolution of septal penetration (DSP) for improving quantification in (123)I cardiac single photon emission computed tomography (SPECT). METHODS: Distance-dependent point spread functions were measured for low-energy high-resolution collimators on a dual-head SPECT system. The measured point spread functions were used in two-dimensional (2-D) and three-dimensional (3-D) models of the collimator response, respectively. 2-D DSP and 3-D DSP were then developed and implemented using iterative reconstruction. A cardiac torso phantom with an internal calibration source was designed with various heart-to-calibration ratios (HCRs) simulating different levels of a patient's uptake. SPECT acquisitions of the phantom were performed using optimized acquisition and processing parameters for (123)I cardiac SPECT. HCRs were calculated using planar projection and tomographic reconstructions. The paired t-test and regression analysis were used to compare the HCRs given by different calculation methods. RESULTS: SPECT produced more accurate HCRs than planar imaging. The slopes of the regression lines for SPECT using filtered back-projection were statistically significantly higher than those for planar imaging (0.2118 +/- 0.0297 vs. 0.0819 +/- 0.0070, P = 0.0001). 2-D DSP and 3-D DSP yielded similar HCRs that were close to the true HCR. The slopes of the regression lines for 2-D DSP and 3-D DSP were 0.9203 +/- 0.0523 and 0.9101 +/- 0.0304, respectively. The DSP HCRs were significantly more accurate than those calculated without DSP (P < 0.0001). CONCLUSION: DSP significantly improves quantification in (123)I cardiac SPECT imaging. 2-D DSP with its less computational burden shows promise for implementation in clinical practice so as to allow the use of the widely available low-energy, high-resolution collimators for quantitative I cardiac SPECT imaging.

Apical hypertrophy caused by glycogen storage disease creating artifacts in myocardial perfusion imaging.

A 46-year-old man with atrial fibrillation and coronary artery disease was referred for myocardial perfusion imaging for the evaluation of chest pain. The patient underwent adenosine stress and rest dual-isotope myocardial perfusion imaging. There was no adenosine-induced chest pain or EKG changes specific for ischemia. Myocardial perfusion images demonstrated an apical "hot spot" and decreased tracer activity in the base of the heart. The polar plots showed a bright center with a rim of significant (>2.5 SD) defect around the base of the myocardium. Ischemia in the base of the heart, with the apex of the heart seemingly normal, was rather puzzling and correlation with magnetic resonance images (MRI) showed apical hypertrophy. Examination of the history revealed that the patient was diagnosed with restrictive cardiomyopathy 2 years ago and endocardial biopsy showed intramyocardial glycogen on electron microscopy, suggesting glycogen storage disease. The case illustrates a "hot spot" resulting from apical hypertrophy creating artifactual fixed defects in myocardial perfusion images and in polar maps.

Standardized Added Metabolic Activity Predicts Survival After Intra-arterial Resin-Based 90Y Radioembolization Therapy in Unresectable Chemorefractory Metastatic Colorectal Cancer to the Liver.

PURPOSE: Standardized added metabolic (SAM) activity is a functional objective measurement of the total tumoral metabolic activity that avoids partial volume effect and thresholding, which limit conventional PET parameters. The purpose of this study is to investigate the role of SAM in predicting survival in unresectable, chemorefractory colorectal hepatic metastatic disease treated with resin-based Y radioembolization. MATERIALS AND METHODS: This is a prospective correlative study of patients with unresectable, chemorefractory colorectal liver metastasis who underwent F-FDG PET/CT and CT/MRI before and after Y. Target RECIST, PERCIST, change in total glycolytic activity (ΔTGA), and ΔSAM treatment response were assessed. Percentage changes in diameter, SUVpeak, TGA, and SAM were calculated pre- and post-Y therapy and objective response was defined as >30% change (responders). Survival analysis by Kaplan-Meier, log-rank, and Cox proportional hazard models were performed and significance was set at <0.05. RESULTS: Sixteen patients (mean age of 61.6) were enrolled and performed a total of 20 Y therapies. After Y, target ΔSAM showed an objective response rate of 40% vs. 35%, 30%, and 22.2% based on target ΔTGA, PERCIST, and RECIST criteria, respectively. Median overall survival (OS) of the cohort after Y was 9.2 months (CI 95% 2.2-16.2). Patients demonstrating objective response based on ΔSAM had a median OS of 22.7 months (CI 95% 12.4-33.0) vs. 6.7 (CI 95% 4.2-9.2) in non-responders (P = 0.007). On multivariate analysis, hazard ratios for the objective response group based on target ΔSAM were 0.01 (P = 0.03) vs. 0.05 (P = 0.08), 0.20 (P = 0.29), and 0.91 (P = 0.98) based on target ΔTGA, PERCIST, and RECIST criteria, respectively. CONCLUSIONS: In unresectable colorectal liver metastatic disease refractory to standard chemotherapy, ΔSAM predicted OS for assessment of response following Y radioembolization therapy, whereas RECIST, PERCIST, and ΔTGA did not.

Is there a role for PET/CT parameters to differentiate thyroid cartilage invasion from penetration?

BACKGROUND: Assessment of thyroid cartilage invasion (tumor extension through inner cortex) and thyroid cartilage penetration (tumor involving both the inner and outer cortices of thyroid cartilage) may be challenging with CT (Computed Tomography) and MR imaging (Magnetic Resonance Imaging). Positron Emission Tomography/Computed Tomography (PET/CT) is a non invasive imaging modality that provides both anatomic and metabolic information. Quantitative data obtained from PET/CT, also known as PET/CT parameters, include maximum, mean or peak standardized uptake values (SUVmax, SUVmean, SUVpeak), metabolic tumor volume (MTV), total lesion glycolysis (TLG), standardized added metabolic activity (SAM) and normalized standardized added metabolic activity (NSAM). Our aim was to examine if FDG PET/CT parameters could differentiate thyroid cartilage invasion from penetration. METHODS: 50 patients who underwent PET/CT before laryngectomy for squamous cell carcinoma of the larynx, had SUVmax, SUVmean, SUVpeak, TLG, MTV, SAM and NSAM calculated on a dedicated workstation. Univariate and multivariate analysis was performed. ROC analysis was used to determine the ability of PET/CT parameters to predict pathologically proven thyroid cartilage invasion or penetration. RESULTS: Of the 50 patients, 50% (25/50 patients) had history of prior radiation therapy. Among the previously irradiated group, 24% had thyroid cartilage invasion and penetration. 8% of the patients in this group had thyroid cartilage invasion only. Among the non-irradiated group, 76% had thyroid cartilage invasion and penetration, 8% had thyroid cartilage invasion without penetration. ROC analysis revealed that none of the PET/CT parameters had enough power to predict thyroid cartilage penetration, but TLG, MTV and SAM had enough power to predict thyroid cartilage invasion in non-irradiated patients. TLG, MTV, SAM and NSAM had enough power to predict thyroid cartilage invasion and penetration in irradiated group. CONCLUSION: TLG, MTV and SAM have enough power to predict thyroid cartilage invasion and penetration in irradiated patients. PET/CT parameters do not have enough potential to differentiate thyroid cartilage invasion from penetration.