High-Output Heart Failure in Multiple Myeloma: Novel Application of Tc-99m MAA to Identify Intramedullary Shunting.

We introduce the innovative use of technetium-99m-labeled macroaggregated albumin to diagnose high-output heart failure in a patient with multiple myeloma with persistent congestion symptoms. Symptom resolution occurred with lenalidomide and steroids. This marks the first clinical use of technetium-99m-labeled macroaggregated albumin for clarifying high-output heart failure etiology.

Remote Reading and Teaching of Nuclear Medicine in the Era of COVID-19.

Community SARS-CoV-2 has profoundly affected traditional elements of learning and teaching in nuclear medicine and diagnostic radiology departments. The response of the nuclear medicine community to the challenges imposed by the COVID-19 pandemic can be described in 3 phases: accommodation, consolidation and optimization, and a return towards normalcy. Adoption of virtual communication platforms has emerged as the crucial interim tool for preservation of trainee supervision and diagnostic imaging education. Development of supplemental teaching materials, refocusing research interests, and relaxation of requirements have all contributed toward stabilization of the residency programs. As we embark on a gradual return to normalcy, many of the virtual solutions that were employed have gained a degree of enduring popularity and may find a place in the postpandemic period.

Experience with a Perfusion-Only Screening Protocol for Evaluation of Pulmonary Embolism During the COVID-19 Pandemic Surge.

The purpose of this study was to evaluate a pulmonary embolism (PE) perfusion-only screening (POS) protocol introduced during the coronavirus disease 2019 (COVID-19) pandemic surge. Subjects without dense parenchymal lung opacities were studied; those with less than 1 segmental perfusion defect were considered to have no PE, whereas those exhibiting 1 or more defects were indeterminate, mandating additional examinations to determine the final diagnosis. Methods: We analyzed demographic information, clinical data, imaging findings, and follow-up data from the electronic records of COVID-19 patients who underwent lung scintigraphy during the 60-d study period. Results: In total, 53 studies were performed on 17 COVID-19-positive and 36 COVID-19-negative patients. The POS protocol efficiently excluded PE in 79% of cases; the remaining 21%, indeterminate for PE, were generally referred for alternative testing or were directly anticoagulated. In patients with negative POS results, there was a very low mortality before hospital discharge (1/42) and normal results on follow-up studies (6/6). Conclusion: The POS protocol, implemented during the COVID-19 surge, efficiently and safely excluded PE in 79% of patients.

Radioimmunotherapy of non-Hodgkin's lymphoma: from the 'magic bullets' to 'radioactive magic bullets'.

Radioimmunotherapy (RIT) of lymphoma with Zevalin and Bexxar was approved by FDA in 2002 and 2003, respectively, for the treatment of relapsed or refractory CD20+ follicular B-cell non-Hodgkin´s lymphoma. In 2009, Zevalin was also approved for consolidation therapy in patients with follicular non-Hodgkin's lymphoma that achieve a partial or complete response to first-line chemotherapy. For follicular lymphoma patients, the overall response and progression-free survival rates have significantly improved since the implementation of RIT. The predominant complication of RIT is hematological toxicity that is usually manageable. There are ongoing trials to further define the expanding role of RIT as first line or concomitant therapy in the treatment of lymphoma as well as for certain antibiotic resistant infections and aggressive malignancies. There is also growing interest in the development of newer protocols for increased and more uniform dose delivery resulting in better outcomes and improved patient survival. This review will primarily focus on the role of RIT in treatment of non-Hodgkin's lymphoma, which is of established clinical utility and FDA approved. The mechanism of RIT, available radionuclides and pharmacokinetics, therapy administration, clinical utility and toxicities, and future directions would be discussed.

Diagnostic Performance of Pulmonary Embolism Imaging in Patients with History of Asthma.

Asthma and pulmonary embolism (PE) can present with overlapping symptoms, and distinguishing between these 2 conditions can be challenging. Asthma may limit imaging for PE because of either worsened ventilation defects on ventilation-perfusion scanning (VQ) or increased motion artifacts on CT pulmonary angiography (CTPA). Methods: We identified adults evaluated for PE with VQ or CTPA from 2012 to 2016. Patients with chronic lung disease (other than asthma) were excluded. Studies were classified as negative, positive, or nondiagnostic. Follow-up of negative cases was reviewed to determine the rate of repeat exams (within 1 wk) and the false-negative rate (defined as diagnosis of venous thromboembolism within 90 d). Results: We reviewed 19,412 adults (aged 52 ± 18 y, 70% women) evaluated for PE (60% with VQ, 40% with CTPA); 23% had a history of asthma. Nondiagnostic results were comparable for those with and without asthma for both VQ (asthma, 3.3%; nonasthma, 3.8%; P = 0.223) and CTPA (asthma, 1.6%; nonasthma, 1.5%; P = 0.891). A history of asthma was not associated with a higher rate of repeat exams after negative imaging for VQ (asthma, 1.9%; nonasthma, 2.1%; P = 0.547) or CTPA (asthma, 0.6%; nonasthma, 0.6%; P = 0.796), nor was a history of asthma associated with a higher false-negative rate for VQ (asthma, 0.4%; nonasthma, 0.9%; P = 0.015) or CTPA (asthma, 1.9%; nonasthma 1.5%; P = 0.347). Conclusion: A history of asthma in the preceding 10 y was not associated with impaired diagnostic performance of PE imaging for either VQ or CTPA.

Gallium-67 Single-Photon Emission Computed Tomography Affects Management of Infections of Left Ventricular Assist Devices.

Our institution employs gallium-67 single-photon emission computed tomography low-dose CT (Ga-SPECT-CT) to determine the presence and extent of left ventricular assist device (LVAD) infections. We present a retrospective single-center study of 41 LVAD recipients who underwent Ga-SPECT-CT from January 2011 to June 2018 to determine whether Ga-SPECT-CT led to changes in antimicrobial therapy, LVAD revision or exchange, or application for 1A exception. The average age was 56.6 years, predominantly male (80.5%) and diabetic (68.3%), divided between ischemic (48.8%) and nonischemic (51.2%) cardiomyopathy. The majority had HeartMate II devices (82.9%). Device-related infections were classified as possible (12.2%), probable (36.6%), proven (36.6%), or rejected (14.6%). Sensitivity was 68.6% and specificity was 100%. Most VAD-specific infections were percutaneous deep driveline infections (DRIs) (34.1%), and VAD-related infections were primarily bloodstream infections (31.7%). Staphylococcus aureus was the major pathogen isolated. Gallium-67 single-photon emission computed tomography low-dose CT resulted in changes in management in more than half (53.7%) of patients: starting (24.4%) or stopping (17.1%) antimicrobial therapy, LVAD revision (22.0%) or exchange (12.2%), and the application for 1A exception for transplant listing (17.1%). We conclude that Ga-SPECT-CT is an effective modality for determining the presence and extent of LVAD DRIs, and contributed to a change in management in more than half of cases.

Impact of Patient-Centered Care on the Patient Experience in Nuclear Medicine.

OBJECTIVE: To quantify the impact of direct patient-physician interaction within a nuclear medicine pretherapy consultation clinic on the patient experience. METHODS: Patients were asked to complete a survey before and after meeting with the nuclear medicine physician. During each visit, the physician provided disease-specific information, discussed the planned therapy, answered questions, and provided tip sheets and checklists to prepare the patient for therapy. RESULTS: Thirty-eight patients were included in the analysis. Before consultation, 17 patients (44.7%) were "somewhat" or "extremely" familiar with the term "nuclear medicine doctor," whereas after the consultation, 33 patients (86.8%) were "somewhat" or "extremely" familiar with the term "nuclear medicine doctor" (P < 0.001). Thirteen patients (37.1%) felt they had either no understanding or a vague understanding of the therapy and no understanding of the plan for follow-up before the consultation, whereas 2 patients (5.4%) chose this response after the consultation (P < 0.001). More patients responded that they felt "generally" or "perfectly calm" toward the therapy overall after their consultation: 26 patients (68.4%) before vs 34 patients (91.9%) after consultation (P < 0.001). DISCUSSION: Patient- and family-centered care in radiology includes direct physician participation in care delivery. In this report, we evaluate and measure the impact of our nuclear medicine pretherapy consultation clinic on the patient experience. We demonstrate significant impact of direct patient-physician encounters on patient anxiety, patient knowledge of the role of the nuclear medicine physician, and overall patient understanding of their treatment plan.

Performance of Low-Dose Perfusion Scintigraphy and CT Pulmonary Angiography for Pulmonary Embolism in Pregnancy.

BACKGROUND: The symptoms of normal pregnancy overlap those of pulmonary embolism (PE). Limited literature suggests that low-dose perfusion scanning (LDQ), which yields lower maternal-fetal radiation exposure than CT pulmonary angiography (CTPA), performs well in excluding PE in pregnant patients. METHODS: We performed a retrospective cohort study of sequential pregnant women who underwent imaging for PE with LDQ or CTPA between 2008 and 2013 at Montefiore Medical Center. Our practice recommends LDQ for patients with negative results on chest radiographs. Patients were categorized according to initial imaging modality, and a subgroup analysis was performed in patients with asthma. The primary outcome was the negative predictive value (NPV) of imaging determined by VTE diagnosis within 90 days. RESULTS: Of 322 pregnant women (mean age, 27.3 ± 6.3 years), initial imaging was positive for PE in 2.7% (6 of 225) of LDQs and 4.1% (4 of 97) of CTPAs, negative in 88.0% (198 of 225) of LDQs and 86.6% (84 of 97) of CTPAs, and indeterminate/nondiagnostic in 9.3% (21 of 225) of LDQs and 9.3% (9 of 97) of CTPAs (P = .79). Ten patients (3.1%) were treated for PE. The NPV was 100% for LDQ and 97.5% for CTPA. Subgroup analysis of patients with asthma (23.9% of this population) revealed a high likelihood of a negative study in the LDQ and CTPA groups (74.1% and 87.0%, respectively) and 100% NPV for both modalities. CONCLUSIONS: PE is an uncommon diagnosis in pregnancy. LDQ and CTPA perform well, with less maternal-fetal radiation exposure with LDQ. Therefore, when available, LDQ is a reasonable first-choice modality for suspected PE in pregnant women with a negative result on chest radiograph.

Positherapy: targeted nuclear therapy of breast cancer with 18F-2-deoxy-2-fluoro-D-glucose.

Breast cancer remains a major cause of cancer death in women in the United States. Novel therapies are needed for patients when standard treatments are ineffective. We have recently shown on a cellular level the therapeutic potential of positrons in malignancy. Here, we report for the first time positron therapy with (18)F-2-deoxy-2-fluoro-D-glucose ((18)F-FDG) in a breast cancer animal model to affect tumor growth rate and survival (positherapy). We used xenografted mammary tumors in nude mice using Notch mammary cancer cells which also express ras oncogene. Notch xenografted tumors actively took up (18)F-FDG with a tumor to normal tissue ratio of 3.24. Tumor-bearing mice were treated with 2.5 mCi (18)F-FDG, which is equivalent to the physiological human maximum tolerated dose. Positherapy resulted in both significant prolongation of survival and decrease in tumor growth rate in comparison with nontreated controls. Immunoblot of Notch tumors showed the presence of glucose transporters (GLUT) 1, 4, and 8. Substantial differences between GLUT1, GLUT4, and GLUT8 were observed in their distribution within the tumor mass. Whereas GLUT4 and GLUT8 were distributed relatively homogeneously throughout the tumor, GLUT1 was confined to necrotic areas. Immunofluorescence double labeling was used to determine cellular localization of GLUTs. GLUT1 was expressed mostly at the cell membrane. GLUT4 and GLUT8 were mostly localized to cytoplasmic compartments with some GLUT4 expressed at or near the cell membrane in close proximity to GLUT1. Thus, GLUT1 was likely responsible for the (18)F-FDG uptake by tumor cells with some possible contribution from GLUT4. These results are important for the development of positherapy with (18)F-FDG for refractory metastatic breast and other cancers.

Preoperative 18F-FDG-PET/CT vs Contrast-Enhanced CT to Identify Regional Nodal Metastasis among Patients with Head and Neck Squamous Cell Carcinoma.

Objective Our objective was to compare the accuracy of preoperative positron emission tomography (PET)/computed tomography (CT) and contrast-enhanced CT (CECT) in detecting cervical nodal metastases in patients treated with neck dissection and to scrutinize the ability of each modality to determine nodal stage. Study Design Case series with chart review. Setting Montefiore Medical Center, Bronx, New York. Subjects and Methods Patients who underwent neck dissection at our institution for primary treatment of head and neck squamous cell carcinoma (HNSCC) and had received preoperative PET/CT and CECT were included in this study. Imaging studies were reinterpreted by 3 specialists within the field and compared for interreader agreement. Concordance between radiology and histopathology was measured using neck levels and sides, along with patient nodal stage. Sensitivity, specificity, accuracy, positive predictive value, negative predictive value, and agreement coefficients were calculated. Results Seventy-three patients were included in the study. Sensitivity was 0.69 and 0.94 (level and side) for PET/CT vs 0.53 and 0.66 for CECT ( P = .056, P = .001). Specificity was 0.86 and 0.56 for PET/CT vs 0.91 and 0.76 for CECT ( P = .014, P = .024). No significant difference was found in overall accuracy ( P = .33, P = .88). The overall agreement percentages between N stage called by imaging modality and pathology were 52% and 55% for PET/CT and CECT, respectively. Conclusion No significant difference in sensitivity was found between PET/CT and CECT. CECT was found to have superior specificity compared with PET/CT. The information gleaned from each modality in the pretreatment evaluation of HNSCC appears to be complementary.

Using the intraoperative hand held probe without lymphoscintigraphy or using only dye correlates with higher sensory morbidity following sentinel lymph node biopsy in breast cancer: a review of the literature.

BACKGROUND: There are no studies that have directly investigated the incremental reduction in sensory morbidity that lymphoscintigraphy images (LS) and triangulated body marking or other skin marking techniques provide during sentinel lymph node biopsy (SLNB) compared to using only the probe without LS and skin marking or using only dye. However, an indirect assessment of this potential for additional sensory morbidity reduction is possible by extracting morbidity data from studies comparing the morbidity of SLNB to that of axillary lymph node dissection. METHODS: A literature search yielded 13 articles that had data on sensory morbidity at specific time points on pain, numbness or paresthesia from SLNB that used radiotracer and probe or used only dye as a primary method of finding the sentinel node (SN). Of these, 10 utilized LS, while 3 did not utilize LS. By matching the data in studies not employing LS to the studies that did, comparisons regarding the percentage of patients experiencing pain, numbness/paresthesia after SLNB could be reasonably attempted at a cutoff of 9 months. RESULTS: In the 7 studies reporting on pain after 9 months (> 9 months) that used LS (1347 patients), 13.8% of patients reported these symptoms, while in the one study that did not use LS (143 patients), 28.7% of patients reported these symptoms at > 9 months (P < 0.0001). In the 6 studies reporting on numbness and/or paresthesia at > 9 months that used LS (601 patients), 12.5% of patients reported these symptoms, while in the 3 studies that did not use LS (229 patients), 23.1% of patients reported these symptoms at > 9 months (P = 0.0002). Similar trends were also noted for all these symptoms at < or = 9 months. CONCLUSION: Because of variations in techniques and time of assessing morbidity, direct comparisons between studies are difficult. Nevertheless at a minimum, a clear trend is present: having the LS images and skin markings to assist during SLNB appears to yield more favorable morbidity outcomes for the patients compared to performing SLNB with only the probe or performing SLNB with dye alone. These results are extremely pertinent, as the main reason for performing SLNB itself in the first place is to achieve reduced morbidity.

Lymphoscintigraphy and triangulated body marking for morbidity reduction during sentinel node biopsy in breast cancer.

Current trends in patient care include the desire for minimizing invasiveness of procedures and interventions. This aim is reflected in the increasing utilization of sentinel lymph node biopsy, which results in a lower level of morbidity in breast cancer staging, in comparison to extensive conventional axillary dissection. Optimized lymphoscintigraphy with triangulated body marking is a clinical option that can further reduce morbidity, more than when a hand held gamma probe alone is utilized. Unfortunately it is often either overlooked or not fully understood, and thus not utilized. This results in the unnecessary loss of an opportunity to further reduce morbidity. Optimized lymphoscintigraphy and triangulated body marking provides a detailed 3 dimensional map of the number and location of the sentinel nodes, available before the first incision is made. The number, location, relevance based on time/sequence of appearance of the nodes, all can influence 1) where the incision is made, 2) how extensive the dissection is, and 3) how many nodes are removed. In addition, complex patterns can arise from injections. These include prominent lymphatic channels, pseudo-sentinel nodes, echelon and reverse echelon nodes and even contamination, which are much more difficult to access with the probe only. With the detailed information provided by optimized lymphoscintigraphy and triangulated body marking, the surgeon can approach the axilla in a more enlightened fashion, in contrast to when the less informed probe only method is used. This allows for better planning, resulting in the best cosmetic effect and less trauma to the tissues, further reducing morbidity while maintaining adequate sampling of the sentinel node(s).

Positron emission tomography agent 2-deoxy-2-[18F]fluoro-D-glucose has a therapeutic potential in breast cancer.

BACKGROUND: Novel approaches are needed for breast cancer patients in whom standard therapy is not effective. 2-Deoxy-2-[18F]fluoro-D-glucose (18F-FDG) was evaluated as a potential radiomolecular therapy agent in breast cancer animal models and, retrospectively, in patients with metastatic breast cancer. METHODS: Polyoma middle T antigen (PyMT) and mouse mammary tumor virus-NeuT transgenic mice with tumors 0.5-1 cm in diameter were imaged with 18F-FDG, and tumor to liver ratios (TLRs) were calculated. The radiotoxicity of 18F-FDG administration was determined in healthy mice. PyMT mice with small (0.15-0.17 cm) and large (more than 1 cm) tumors were treated with 2-4 mCi of 18F-FDG, and control C3H/B6 mice with 3 mCi of 18F-FDG. At 10 days after treatment the tumors and control mammary glands were analyzed for the presence of apoptotic and necrotic cells. Five patients with breast cancer and metastatic disease were evaluated and standardized uptake values (SUVs) in tumors, maximum tolerated dose, and the doses to the tumor were calculated. RESULTS: Doses up to 5 mCi proved to be non-radiotoxic to normal organs. The 18F-FDG uptake in mouse tumors showed an average TLR of 1.6. The treatment of mice resulted in apoptotic cell death in the small tumors. Cell death through the necrotic pathway was seen in large tumors, and was accompanied by tumor fragmentation and infiltration with leukocytes. Normal mammary tissues were not damaged. A human 18F-FDG dose delivering 200 rad to the red marrow (less than 5% damage) was calculated to be 4.76 Ci for a 70 kg woman, and the dose to the tumors was calculated to be 220, 1100 and 2200 rad for SUVs of 1, 5 and 10, respectively. CONCLUSION: We have shown that positrons delivered by 18F-FDG to mammary tumors have a tumoricidal effect on cancer cells. The study of breast cancer patients suggests that the tumor and normal organ dosimetry of 18F-FDG makes it suitable for therapy of this malignancy.