Remodelado del ventrículo izquierdo postinfarto: una mirada desde la perfusión miocárdica gated-SPECT / Left Ventricular Remodeling After Myocardial Infarction: A Perspective from Gated-SPECT Myocardial Perfusion Imaging

RESUMEN Introducción: El estudio gatillado de perfusión miocárdica con tomografía computarizada por emisión de fotón único, o gated-SPECT (por su denominación en inglés) es un método apropiado para cuantificar la magnitud de la escara necrótica y establecer su territorio. El análisis de pacientes con infartos de pequeña y mediana extensión que evolucionan con deterioro de la fracción de eyección ventricular izquierda (FEVI), podría arrojar luz acerca de los factores que influyen en la presencia de remodelado adverso y la consiguiente evolución a disfunción ventricular. Objetivos: a) evaluar la prevalencia de FEVI disminuida y factores asociados en una población de pacientes derivados para estudios de gated-SPECT, y b) definir la prevalencia de remodelado adverso y factores asociados en el subgrupo de pacientes con carga necrótica intermedia a baja. Material y métodos: Realizamos un análisis retrospectivo de pacientes consecutivos que se realizaron gated-SPECT durante el año 2017. Se excluyeron los pacientes con enfermedad valvular significativa o arritmias que produjeran alteración del gatillado. Se consideró remodelado adverso a la conjunción de FEVI disminuida (FEVI < 50%) y porcentaje de miocardio necrótico menor que 20 %. Resultados: Se incluyeron 1902 pacientes. La prevalencia de FEVI disminuida fue del 8 % (n =148). En el análisis multivariado, las variables independientes asociadas a disfunción ventricular fueron el género masculino (OR 2,50; IC 95% 1,30-4,90, p = 0,005), la diabetes (OR 1,83; IC 95% 1,12-3, p = 0,01), y compromiso necrótico mayor que 6,6 % (OR 39 IC 95% 25-61,28, p = 0,00001). En el subgrupo de pacientes con carga necrótica menor que 20% (n =197), la prevalencia de remodelado adverso fue del 25% (n =50). El análisis multivariado arrojó que la diabetes (OR 2,83; IC 95% 1,31 - 6,10 p = 0,007) y el género masculino (OR 5; IC 95% 1,10 - 22,9 p = 0,007) presentaron asociación independiente con el remodelado adverso. Conclusión: La gated-SPECT podría utilizarse en la valoración del remodelado adverso y factores asociados. Dicha valoración surge de la combinación de variables que no requieren un software adicional y se usan en la práctica diaria.

ABSTRACT Background: Gated single-photon emission computed tomography (gated-SPECT) myocardial perfusion imaging is a suitable technique for measuring the infarct scar size and defining its territory. Analyzing patients with small and medium myocardial infarctions that develop reduced left ventricular ejection fraction (LVEF) could provide additional information of the factors that contribute to adverse remodeling and its outcome. Objectives: a) To evaluate the prevalence of reduced LVEF and associated factors in a population of patients referred for gated-SPECT imaging, and b) to define the prevalence of adverse remodeling and associated factors in the subgroup of patients with intermediate to low necrotic burden. Methods: We conducted a retrospective analysis of consecutive patients undergoing gated-SPECT imaging during 2017. Patients with significant valvular heart disease or arrhythmias that could difficult adequate ECG gating were excluded from the study. Adverse remodeling was considered as the combination of reduced LVEF (LVEF < 50%) with percent myocardium scar < 20%. Results: A total of 1902 patients were included. The prevalence of reduced LVEF was 8% (n = 148). On multivariate analysis, the variables with independent association with ventricular dysfunction were male sex (OR 2.50; 95% CI 1.30-4.90, p = 0.005), diabetes (OR 1.83; 95% CI 1.12-3, p = 0.01), and percent myocardium scar > 6.6 % (OR 39; 95% CI 25-61.28, p = 0.00001). In the subgroup of patients with scar burden < 20 % (n = 197), the prevalence of adverse remodeling was 25 % (n = 50). On multivariate analysis, diabetes (OR 2.83; 95% CI 1.31 - 6.1 p = 0.007) and male sex (OR 5; 95% CI 1.1 - 22.9, p = 0.007) showed an independent association with adverse remodeling. Conclusion: Gated-SPECT could be used to assess adverse remodeling and its associated factors. This assessment is the result of combining variables used in daily practice which do not require any additional software.

The role of brain perfusion SPECT in the diagnosis of frontotemporal dementia: A systematic review.

BACKGROUND AND PURPOSE: Frontotemporal dementia (FTD) is the second most common cause of presenile dementia. The clinical distinction between FTD, Alzheimer's disease (AD), and other dementias is a clinical challenge. Brain perfusion SPECT may contribute to the diagnosis of FTD, but its value is unclear. METHODS: We performed a systematic review to investigate the diagnostic accuracy of the brain SPECT in (1) distinguishing FTD from AD and other dementias and (2) differentiating FTD variants. RESULTS: Overall, 391 studies were retrieved on the initial search and 35 studies composed the final selection, comprising a total number of 3142 participants of which 1029 had FTD. The sensitivity and the specificity for the differential diagnosis of FTD versus AD ranged from 56% to 88% and from 51% to 93%, respectively. SPECT is not superior to the clinical method of diagnosis, but the combination of SPECT with clinical data seems to improve the diagnostic accuracy. CONCLUSION: Brain perfusion SPECT has a limited value in the diagnostic framework of FTD. SPECT can be performed when FDG-PET is not available. SPECT is recommended only for selected cases when the diagnosis is challenging using conventional methods.

Diagnosis of SPECT/CT bone imaging combined with two serum examinations in patients with bone metastases from pulmonary cancer.

PURPOSE: To study the clinical diagnostic value of SPECT/CT bone imaging combined with two serum examinations in patients with bone metastases from pulmonary cancer. METHODS: The clinical data of 120 patients consistent with pulmonary cancer admitted to the First Affiliated Hospital of Hebei North University from March 2019 to December 2019 were selected for retrospective analysis, and they were divided into the bone metastasis group (n = 58) and non-bone metastasis group (n = 62) according to comprehensive evaluation result of X-ray, CT, MRI and clinical follow-up. The CT values of patients were obtained by SPECT/CT bone imaging to compare serum levels of ALP (alkaline phosphatase belongs to phosphoric monoester hydrolases, as a specific phosphatase, mainly in body tissues and body fluid) and BAP (bone alkaline phosphatase is formed by different modification and processing of alkaline phosphatase, and is mainly released by osteoblasts) and CT values of patients in both groups, using receiver operating characteristic (ROC) curve to evaluate the diagnostic efficacy of single detection and combined detection. RESULTS: SPECT/CT bone imaging in patients with bone metastasis from pulmonary cancer showed abnormal radioactive accumulation in spine, pelvis and bilateral ribs. Serum ALP, BAP and CT values in bone metastasis group were overtly higher than the non-bone metastasis group (P < 0.001). Logistic regression analysis showed that serum ALP, BAP and CT value were independent risk factors for bone metastasis from pulmonary cancer. The AUC value and Youden index of combined diagnosis were higher than those of single diagnosis. CONCLUSION: SPECT/CT bone imaging combined with serum detection of ALP and BAP in patients with pulmonary cancer is helpful for early diagnosis of bone metastasis, which provides more basis for the formulation and selection of clinical treatment options.

Impacto Clínico da Avaliação da Reserva de Fluxo Miocárdico na Identificação da Causa do Desconforto Torácico / Clinical Impact of Assessment of Myocardial Flow Reserve in Identifying the Cause of Chest Discomfort

Resumo Fundamento: Gama-câmaras com detectores de telureto-cádmio-zinco (CZT) permitiram a quantificação da reserva de fluxo miocárdico (RFM), podendo aumentar a acurácia da cintilografia miocárdica de perfusão (CMP) para detectar a causa do desconforto torácico. Objetivo: Avaliar o impacto clínico da RFM para detectar a causa do desconforto torácico. Métodos: 171 pacientes com desconforto torácico que foram submetidos a coronariografia ou angiotomografia de coronárias também realizaram CMP e RFM num intervalo de tempo <30 dias. As aquisições das imagens dinâmicas de repouso e estresse foram iniciadas simultaneamente à injeção de 99mTc sestamibi (10 e 30mCi, respectivamente), ambas com duração de onze minutos, seguidas imediatamente pela aquisição das imagens de perfusão durante 5 minutos. O estresse foi realizado com dipiridamol. Uma RFM global ou por território coronariano <2,0 foi classificada como anormal. Resultados: A idade média foi de 65,9±10 anos (60% do sexo feminino). A avaliação anatômica mostrou que 115 (67,3%) pacientes apresentavam obstrução coronariana significativa, sendo que, 69 apresentavam CMP anormal e 91 apresentavam RFM anormal (60,0% vs. 79,1%, p<0,01). Dentre os pacientes sem obstrução (56 - 32,7%), 7 tinham CMP anormais e 23 tinham RFM global reduzida. A realização da RFM identificou a etiologia do desconforto torácico em 114 pacientes enquanto a CMP identificou em 76 (66,7% vs. 44,4%, p<0,001). Conclusão: A RFM é uma medida fisiológica quantificável que aumenta o impacto clínico da CMP na detecção da causa do desconforto torácico através de uma maior acurácia para detecção de DAC obstrutiva e ainda possibilita identificar a presença de doença microvascular.

Abstract Background: Gamma cameras with cadmium-zinc telluride (CZT) detectors allowed the quantification of myocardial flow reserve (MBF), which can increase the accuracy of myocardial perfusion scintigraphy (MPS) to detect the cause of chest discomfort. Objective: To assess the clinical impact of MBF to detect the cause of chest discomfort. Methods: 171 patients with chest discomfort who underwent coronary angiography or coronary CT angiography also underwent MPS and MBF in a time interval of <30 days. The acquisitions of dynamic imaging of rest and stress were initiated simultaneously with the 99mTc injection sestamibi (10 and 30mCi, respectively), both lasting eleven minutes, followed by immediately acquiring perfusion images for 5 minutes. The stress was performed with dipyridamole. A global or per coronary territory MBF <2.0 was classified as abnormal. Results: The average age was 65.9±10 years (60% female). The anatomical evaluation showed that 115 (67.3%) patients had coronary obstruction significant, with 69 having abnormal MPs and 91 having abnormal MBF (60.0% vs 79.1%, p<0.01). Among patients without obstruction (56 - 32.7%), 7 had abnormal MPS, and 23 had reduced global MBF. Performing MBF identified the etiology of the chest discomfort in 114 patients while MPS identified it in 76 (66.7% vs 44.4%, p<0.001). Conclusion: MBF is a quantifiable physiological measure that increases the clinical impact of MPS in detecting the cause of chest discomfort through greater accuracy for detecting obstructive CAD, and it also makes it possible to identify the presence of the microvascular disease.

SPECT/CT con 99mTc-pirofosfato en la evaluación de la amiloidosis cardíaca: estudio preliminar / SPECT/CT with 99mTc-pyrophosphate in the evaluation of cardiac amyloidosis: a preliminary study / SPECT/CT com pirofosfato de 99mTc na avaliação de amiloidose cardíaca: estudo preliminar

Introducción: la amiloidosis cardíaca (AC) es una miocardiopatía infiltrativa producida por depósito miocárdico extracelular de amiloide. Las variantes más frecuentes son debidas a cadenas ligeras de inmunoglobulinas o transtiretina (ATTR). El centellograma con 99mTc-pirofosfato (99mTc-PYP) es una técnica de imagen molecular que permite diferenciar los subtipos más frecuentes de AC. El presente estudio analizó el rol del 99mTc-PYP y el SPECT-CT en la evaluación de pacientes con sospecha clínica de AC. Materiales y métodos: se realizó 99mTc-PYP y SPECT-CT en 16 pacientes con sospecha clínica de AC, con edad promedio de 63 años. Se realizó análisis cualitativo de las imágenes planares y del SPECT-CT (Mediso, AnyScan), adquiridas 1-3 horas tras la inyección del radiotrazador. Para el análisis cuantitativo de las imágenes planares se calculó la relación H/CL (cuentas promedio obtenidas sobre las regiones de interés del corazón y el hemitórax contralateral). El estudio se consideró positivo para ATTR cuando la relación H/CL fue ≥1.5. Las imágenes de SPECT-CT fueron interpretadas para observar la distribución del trazador a nivel cardíaco y extracardíaco. Resultados: se identificó captación miocárdica de 99mTc-PYP en el ventrículo izquierdo en 6 pacientes y en el ventrículo derecho en 3 pacientes. En estos casos, la relación H/CL fue >1.5. En el resto se descartó la captación miocárdica, con relación H/CL<1.5. Se detectó actividad de pool vascular en las imágenes tomográficas de 7 pacientes y captación extracardíaca ósea anormal de causas traumáticas/degenerativas en 9 pacientes. Cinco pacientes presentaron captación hepática difusa, sin alteración estructural en el TC. Conclusiones: el 99mTc-PYP es una técnica clínicamente relevante en pacientes con sospecha de AC. Constituye una herramienta mínimamente invasiva, ampliamente disponible, de bajo costo y útil en el diagnóstico, pudiendo orientar al subtipo de AC. La información que aporta permite además orientar las opciones terapéuticas y brindar información pronóstica adicional.

Introduction: Cardiac amyloidosis (CA) is an infiltrative cardiomyopathy caused by extracellular myocardial amyloid deposition. The most frequent variants are due to immunoglobulin light chains or transthyretin (ATTR). 99mTc-pyrophosphate (99mTc-PYP) scintigraphy is a molecular imaging technique that allows differentiation of the most common subtypes of AC. The present study analyzed the role of 99mTc-PYP and SPECT-CT in the evaluation of patients with clinical suspicion of CA. Materials and methods: 99mTc-PYP and SPECT-CT were performed in 16 patients with clinical suspicion of AC, with an average age of 63 years. Qualitative analysis was performed on the planar and SPECT-CT images (Mediso, AnyScan), acquired 1-3 hours after the injection of the radiotracer. For the quantitative analysis of the planar images, the H/CL ratio (average counts obtained over the regions of interest of the heart and the contralateral hemithorax) was calculated. The study was considered positive for ATTR when the H/CL ratio was ≥1.5. The SPECT-CT images were interpreted to observe the distribution of the tracer at the cardiac and extracardiac level. Results: Myocardial uptake of 99mTc-PYP was identified in the left ventricle in 6 patients and in the right ventricle in 3 patients. In these cases, the H/CL ratio was >1.5. In the rest, myocardial uptake was ruled out, with a H/CL ratio of 1.5. Vascular pool activity was detected in the tomographic images of 7 patients and abnormal extracardiac bone uptake of traumatic/degenerative causes in 9 patients. Five patients presented diffuse hepatic uptake, without structural alteration on CT. Conclusions: 99mTc-PYP is a clinically relevant technique in patients with suspected CA. It constitutes a minimally invasive tool, widely available, low cost and useful in diagnosis, and can guide the AC subtype. The information it provides also makes it possible to guide therapeutic options and provide additional prognostic information.

Introdução: a amiloidose cardíaca (AC) é uma cardiomiopatia infiltrativa causada pela deposição extracelular de amiloide no miocárdio. As variantes mais frequentes são devidas a cadeias leves de imunoglobulina ou transtirretina (ATTR). A cintilografia com 99mTc-pirofosfato (99mTc-PYP) é uma técnica de imagem molecular que permite a diferenciação dos subtipos mais comuns de QA. O presente estudo analisou o papel do 99mTc-PYP e do SPECT-CT na avaliação de pacientes com suspeita clínica de AC. Materiais e métodos: foram realizados 99mTc-PYP e SPECT-CT em 16 pacientes com suspeita clínica de QA, com idade média de 63 anos. A análise qualitativa foi realizada nas imagens planas e SPECT-CT (Mediso, AnyScan), adquiridas 1-3 horas após a injeção do radiotraçador. Para a análise quantitativa das imagens planas, foi calculada a relação H/CL (contagens médias obtidas nas regiões de interesse do coração e do hemitórax contralateral). O estudo foi considerado positivo para ATTR quando a relação H/CL era ≥1,5. As imagens SPECT-CT foram interpretadas para observar a distribuição do traçador em nível cardíaco e extracardíaco. Resultados: a captação miocárdica de 99mTc-PYP foi identificada no ventrículo esquerdo em 6 pacientes e no ventrículo direito em 3 pacientes. Nestes casos, a relação H/CL foi >1,5. Nos demais, foi descartada captação miocárdica, com relação H/CL de 1,5. Atividade do pool vascular foi detectada nas imagens tomográficas de 7 pacientes e captação óssea extracardíaca anormal de causas traumáticas/degenerativas em 9 pacientes. Cinco pacientes apresentaram captação hepática difusa, sem alteração estrutural na TC. Conclusões: o 99mTc-PYP é uma técnica clinicamente relevante em pacientes com suspeita de AC. Constitui uma ferramenta minimamente invasiva, amplamente disponível, de baixo custo e útil no diagnóstico, podendo orientar o subtipo AC. A informação que disponibiliza permite também orientar opções terapêuticas e fornecer informação prognóstica adicional.

99mTc-Labeled Cyclic Peptide Targeting PD-L1 as a Novel Nuclear Imaging Probe.

Recent cancer therapies have focused on reducing immune suppression in the tumor microenvironment to prevent cancer progression and metastasis. PD-1 is a checkpoint protein that stops the immune response and is expressed on immune T cells. Cancer cells express a PD-1 ligand (PD-L1) to bind to the T-cell surface and activate immunosuppressive pathways. This study aimed to design, synthesize, and evaluate a 99mTc-labeled PD-L1-targeting cyclic peptide inhibitor (99mTc-iPD-L1) as a novel SPECT radiopharmaceutical for PD-L1 expression imaging. AutoDock software (version 1.5) was used to perform molecular docking for affinity calculations. The chemical synthesis was based on the coupling reaction of 6-hydrazinylpyridine-3-carboxylic acid with a 14-amino-acid cyclic peptide. iPD-L1 was prepared for 99mTc labeling. Radio-HPLC was used to verify radiochemical purity. The stability of the radiopeptide in human serum was evaluated by HPLC. iPD-L1 specificity was assessed by SDS-PAGE. [99mTc]Tc-iPD-L1 cellular uptake in PD-L1-positive cancer cells (HCC827 and HCT116) and biodistribution in mice with induced tumors were also performed. One patient with advanced plantar malignant melanoma received [99mTc]Tc-iPD-L1. The iPD-L1 ligand (AutoDock affinity: -6.7 kcal/mol), characterized by UPLC mass, FT-IR, and UV-Vis spectroscopy, was obtained with a chemical purity of 97%. The [99mTc]Tc-iPD-L1 was prepared with a radiochemical purity of >90%. In vitro and in vivo analyses demonstrated [99mTc]Tc-iPD-L1 stability (>90% at 24 h) in human serum, specific recognition for PD-L1, high uptake by the tumor (6.98 ± 0.89% ID/g at 1 h), and rapid hepatobiliary and kidney elimination. [99mTc]Tc-iPD-L1 successfully detected PD-L1-positive lesions in a patient with plantar malignant melanoma. The results obtained in this study warrant further dosimetric and clinical studies to determine the sensitivity and specificity of [99mTc]Tc-iPD-L1/SPECT for PD-L1 expression imaging.

Diagnostic Performance of 99mTc-iPSMA SPECT/CT in the Initial Staging of Patients with Unfavorable Intermediate-, High-, and Very High-Risk Prostate Cancer: A Comparative Analysis with 18F-PSMA-1007 PET/CT.

Prostate cancer is a leading cause of cancer death in men worldwide. Imaging plays a key role in disease detection and initial staging. Emerging data has shown the superiority of PSMA imaging with PET/CT over conventional imaging for primary diagnoses. Single photon emission computed tomography is more available worldwide, and the imaging agent is low in cost. The aim of this study is to compare the diagnostic accuracy of 99mTc-EDDA/HYNIC-iPSMA SPECT/CT to 18F-PSMA-1007 PET/CT in the primary diagnosis of prostate cancer and the impact on clinical staging. METHODS: In this prospective controlled study, 18 patients with histologically confirmed prostate cancer with unfavorable intermediate-, high-, and very high-risk characteristics were recruited to undergo 18F-PSMA-PET/CT and 99mTc-iPSMA SPECT/CT. The median age of the patients was 71 years old, and the median PSA level was 23.3 ng/mL. Lesions were divided into the prostate, seminal vesicles, lymph nodes, bone, and visceral metastases. Volumetric analysis was also performed between the two imaging modalities and correlated with PSA levels. RESULTS: A total of 257 lesions were detected on 18F-PSMA-PET/CT: prostate (n = 18), seminal vesicles (n = 12), locoregional lymph nodes (n = 62), non-locoregional (n = 67), bone (n = 90), and visceral (n = 8). Of these, 99mTc-iPSMA-SPECT/CT detected 229 lesions, while both reviewers detected 100% of the lesions in the prostate (18/18), seminal vesicles (12/12), and visceral (8/8); LN LR (56/62; 90%), NLR (57/67; 85%), and bone (78/90; 86%). There were no statistically significant differences between volumetric parameters (t = -0.02122; p = 0.491596). CONCLUSIONS: 99mTc-iPSMA SPECT/CT is useful in the primary diagnosis of prostate cancer. Despite it showing a slightly lower lesion detection rate compared to 18F-PSMA PET/CT, it exhibited no impact on clinical staging and, consequently, the initial treatment intention.

Radiochemical and biological assessments of a PSMA-I&S cold kit for fast and inexpensive 99mTc-labeling for SPECT imaging and radioguided surgery in prostate cancer.

The expression of prostate-specific membrane antigen (PSMA) is upregulated in prostate cancer (PCa) cells and PSMA-ligands have been radiolabeled and used as radiopharmaceuticals for targeted radionuclide therapy (TRT), single photon emission computed tomography (SPECT) or positron emission tomography (PET) molecular imaging, and radioguided surgery in PCa patients. Herein, we aimed at radiolabeling the PSMA-I&S cold kit with 99mTc, resulting in a radiopharmaceutical with high radiochemical yield (RCY) and stability for SPECT imaging and radioguided surgery in PCa malignancies. Various pre-clinical assays were conducted to evaluate the [99mTc]Tc-PSMA-I&S obtained by the cold kit. These assays included assessments of RCY, radiochemical stability in saline, lipophilicity, serum protein binding (SPB), affinity for LNCaP-PCa cells (binding and internalization studies), and ex vivo biodistribution profile in naive and LNCaP-PCa-bearing mice. The radiopharmaceutical was obtained with good RCY (92.05% ± 2.20%) and remained stable for 6 h. The lipophilicity was determined to be -2.41 ± 0.06, while the SPB was ∼97%. The binding percentages to LNCaP cells were 9.41% ± 0.57% (1 h) and 10.45% ± 0.45% (4 h), with 63.12 ± 0.93 (1 h) and 65.72% ± 1.28% (4 h) of the bound material being internalized. Blocking assays, employing an excess of unlabeled PSMA-I&S, resulted in a reduction in the binding percentage by 2.6 times. The ex vivo biodistribution profile confirmed high accumulation of [99mTc]Tc-PSMA-I&S in the tumor and the tumor-to-contralateral muscle ratio was ∼6.5. In conclusion, [99mTc]Tc-PSMA-I&S was successfully obtained by radiolabeling the cold kit using freshly eluted [99mTc]NaTcO4, exhibiting good RCY and radiochemical stability. The preclinical assays demonstrated that the radiopharmaceutical shows favorable characteristics for SPECT imaging and radioguided surgery in PCa patients.

Is brain perfusion correlated to switching mood states and cognitive impairment in bipolar disorder type I? A longitudinal study using perfusion imaging approach.

Type I Bipolar disorder (BD-I) is a neuropsychiatric disorder characterized by manic or mixed-featured episodes, impaired cognitive functioning, and persistent work and social functioning impairment. This study aimed to investigate within-subject; (i) differences in brain perfusion using Single-photon emission computed tomography (SPECT) between manic and euthymic states in BD-I patients; (ii) explore potential associations between altered brain perfusion and cognitive status; and (iii) examine the relationship between cerebral perfusion and mania symptom ratings. Seventeen adult patients diagnosed with BD-I in a manic episode were recruited, and clinical assessments, cognitive tests, and brain perfusion studies were conducted at baseline (mania state) and a follow-up visit 6 months later. The results showed cognitive impairment during the manic episode, which persisted during the euthymic state at follow-up. However, no significant changes in brain perfusion were observed between the manic and euthymic states. During mania, trends toward decreased perfusion in the left cerebellum and right superior parietal lobule were noted. Additionally, trends indicated a higher perfusion imbalance in the left superior and middle frontal gyrus during mania and the right superior and middle frontal gyrus during euthymia. No significant correlations existed between brain perfusion, mania symptom ratings, and cognitive performance, indicating that symptomatology might represent more than neural hemodynamics. These findings suggest that cognitive impairment may persist in BD-I patients and highlight the need for therapeutic interventions targeting cognitive deficits. More extensive studies with extended follow-up periods are warranted further to investigate brain perfusion and cognitive functioning in BD-I patients.

Synthetic Attenuation Correction Maps for SPECT Imaging Using Deep Learning: A Study on Myocardial Perfusion Imaging.

(1) Background: The CT-based attenuation correction of SPECT images is essential for obtaining accurate quantitative images in cardiovascular imaging. However, there are still many SPECT cameras without associated CT scanners throughout the world, especially in developing countries. Performing additional CT scans implies troublesome planning logistics and larger radiation doses for patients, making it a suboptimal solution. Deep learning (DL) offers a revolutionary way to generate complementary images for individual patients at a large scale. Hence, we aimed to generate linear attenuation coefficient maps from SPECT emission images reconstructed without attenuation correction using deep learning. (2) Methods: A total of 384 SPECT myocardial perfusion studies that used 99mTc-sestamibi were included. A DL model based on a 2D U-Net architecture was trained using information from 312 patients. The quality of the generated synthetic attenuation correction maps (ACMs) and reconstructed emission values were evaluated using three metrics and compared to standard-of-care data using Bland-Altman plots. Finally, a quantitative evaluation of myocardial uptake was performed, followed by a semi-quantitative evaluation of myocardial perfusion. (3) Results: In a test set of 66 test patients, the ACM quality metrics were MSSIM = 0.97 ± 0.001 and NMAE = 3.08 ± 1.26 (%), and the reconstructed emission quality metrics were MSSIM = 0.99 ± 0.003 and NMAE = 0.23 ± 0.13 (%). The 95% limits of agreement (LoAs) at the voxel level for reconstructed SPECT images were: [-9.04; 9.00]%, and for the segment level, they were [-11; 10]%. The 95% LoAs for the Summed Stress Score values between the images reconstructed were [-2.8, 3.0]. When global perfusion scores were assessed, only 2 out of 66 patients showed changes in perfusion categories. (4) Conclusion: Deep learning can generate accurate attenuation correction maps from non-attenuation-corrected cardiac SPECT images. These high-quality attenuation maps are suitable for attenuation correction in myocardial perfusion SPECT imaging and could obviate the need for additional imaging in standalone SPECT scanners.

A new perspective on an old method: gated SPECT imaging for left ventricular contractile function assessment.

The ejection fraction (LVEF) is a commonly used marker of left ventricular function. However, because it is strongly influenced by loading conditions, it can be inaccurate in representing cardiac contractility. We therefore evaluated a gated SPECT based tool to simultaneously assess preload, afterload, and contractility. Using gated SPECT-determined ventricular volumes and arterial tension measurements, we calculated ventricular and arterial elastance (Ev and Ea), as well as end-diastolic volumes, which are surrogates for contractility, afterload, and preload, respectively. We applied this protocol to 1462 consecutive patients and assessed the ventricular function in patients with and without myocardial infarction. The median LVEF was 68% (IQR 62-74%). Patients with infarction exhibited decreased contractility (ventricular elastance of 3 mmHg/ml vs. 6 mmHg/ml), compensated by an increase of preload (end-diastolic volume of 100 ml vs. 78 ml) and a decrease in afterload (arterial elastance of 1.8 mmHg/ml vs. 2.2 ml/mmHg). These interactions yielded a preserved ejection fraction in both groups. Gated SPECT-measured volumes were consistent with values reported in the literature. In addition, the combination of nuclear imaging and arterial tension measurement accounted for not only the ejection fraction but also the loading context, providing a more accurate representation of cardiac contractility.

A machine learning method integrating ECG and gated SPECT for cardiac resynchronization therapy decision support.

PURPOSE: Cardiac resynchronization therapy (CRT) has been established as an important therapy for heart failure. Mechanical dyssynchrony has the potential to predict responders to CRT. The aim of this study was to report the development and the validation of machine learning models which integrate ECG, gated SPECT MPI (GMPS), and clinical variables to predict patients' response to CRT. METHODS: This analysis included 153 patients who met criteria for CRT from a prospective cohort study. The variables were used to model predictive methods for CRT. Patients were classified as "responders" for an increase of LVEF ≥ 5% at follow-up. In a second analysis, patients were classified as "super-responders" for an increase of LVEF ≥ 15%. For ML, variable selection was applied, and Prediction Analysis of Microarrays (PAM) approach was used to model response while Naïve Bayes (NB) was used to model super-response. These ML models were compared to models obtained with guideline variables. RESULTS: PAM had AUC of 0.80 against 0.72 of partial least squares-discriminant analysis with guideline variables (p = 0.52). The sensitivity (0.86) and specificity (0.75) were better than for guideline alone, sensitivity (0.75) and specificity (0.24). Neural network with guideline variables was better than NB (AUC = 0.93 vs. 0.87) however without statistical significance (p = 0.48). Its sensitivity and specificity (1.0 and 0.75, respectively) were better than guideline alone (0.78 and 0.25, respectively). CONCLUSIONS: Compared to guideline criteria, ML methods trended toward improved CRT response and super-response prediction. GMPS was central in the acquisition of most parameters. Further studies are needed to validate the models.

[99m Tc]Tc-HYNIC-EcgDf21: A defensin short analogue with potential application in infection foci imaging.

Opportunistic infections are a problem of great relevance in public health and the precise detection and localization of infection in the early stages of the disease is of great importance for patient management as well as cost containment. Our proposal seeks to contribute to developing a new agent that meets the needs of diagnosis and follow-up of fungal and bacterial infections, focused on the design of a radiotracer with the potential for recognition of hidden infection foci. Defensins are plant antimicrobial peptides that not only show activity against plant pathogens but also against human ones. A short analogue of EcgDf1 defensin, EcgDf21d (NH2 -ERFTGGHCRGFRRRCFCTKHC-COOH), was labelled through the formation of a 99m Tc-HYNIC complex which was assessed for physicochemical and biological behaviour both in vitro and in vivo. The [99m Tc]Tc-HYNIC-EcgDf21 labelling procedure rendered a single product with remarkably high RCP and stability in the labelling milieu. The Log p value indicated that [99m Tc]Tc-HYNIC-EcgDf21 has a hydrophilic behaviour, confirmed by the biodistribution profiles. The optimal uptake value was obtained for Candida albicans infection model reaching a lesion/muscle ratio of 3, this correlates with in vitro binding studies, and the lesion can be definitely observed in the scintigraphic images.

Diagnosis, performance and added value of assessing ventricular dyssynchrony by phase analysis in patients with three-vessel disease: A single-center cross-sectional study in Mexico.

BACKGROUND: Three-vessel disease (3VD) is a cardiovascular disorder that affects the three main coronary arteries. Gated myocardial perfusion SPECT (GMPS) evaluates ventricular function, synchrony, and myocardial perfusion. However, the diagnostic performance of GMPS parameters to assess 3VD has not been fully explored. AIMS: To assess the univariate performance capacity of GMPS parameters, and to evaluate whether phase parameters could provide additional predictive value for the detection of patients with 3VD compared to control subjects. METHODS: We designed paired retrospective samples of GMPS images of patients with 3VD (stenosis > 70% of left anterior descending, right coronary, and circumflex coronary arteries) and without 3VD. A GMPS in rest-stress protocol was performed using 99mTc-Sestamibi and thallium and analyzed with the 3D method. Area under the receiver-operating characteristic curves (AUROC), decision curve analyses and diagnostic test performance were obtained for univariable analyses and stepwise binomial logistic regression for multivariable performance. RESULTS: 474 Patients were included: 237 with 3VD (84% males, mean age 61.7 ± 9.9 years) and 237 with normal GMPS (51% women, mean age 63.8 ± 10.6 years). The highest AUROC for perfusion parameters were recorded for SSS, SRS and TID. For dyssynchrony parameters, both entropy and bandwidth in rest and stress phases displayed the highest AUROC and diagnostic capacity to detect 3VD. A multivariate model with SRS ≥ 4, SDS ≥ 2, TID > 1.19 and sBW ≥ 48° displayed the highest diagnostic capacity (0.923 [95% CI 0.897-0.923]) to detect 3VD. CONCLUSION: Perfusion and dyssynchrony were the parameters which were most able to discriminate patients with 3VD from those who did not have CAD.

Head-to-head comparison of ventilation/perfusion single photon emission computed tomography/computed tomography and multidetector computed tomography angiography for the detection of acute pulmonary embolism in clinical practice.

INTRODUCTION: Computed tomography angiography (CTA) and ventilation/perfusion (V/Q) single photon emission computed tomography/CT (SPECT/CT) images have been widely used to detect PE, but few studies have performed a direct comparison between them. We aimed to evaluate the performance of these tests in the same group of patients, selected from the routine practice of a general hospital. METHODS: Patients with suspected acute PE were prospectively submitted to CTA and V/Q SPECT/CT. General radiologists and nuclear physicians, respectively, interpreted the images. Data regarding age, sex, time between examinations, symptoms, and Wells score were also recorded. The final diagnosis was decided through a consensus among the clinicians, taking into account clinical, laboratory, follow-up, and all imaging procedures data. RESULTS: Twenty-eight patients (15 male, 13 female, and median age of 51.5 years) were studied. Median duration of the onset of symptoms was 4 (1-14) days, and the median Wells score was 3.5 (1.5-6). Sensitivity, specificity, positive and negative predictive values, and accuracy were 84.6%, 80.0%, 78.6%, 85.7%, and 82.1% for V/Q SPECT/CT, and 46.1%, 100%, 100%, 68.2%, and 75.0% for CTA. The overall agreement between the methods was 57.1%. Of the 22 patients with negative CTA, 10 (45.4%) had positives V/Q SPECT/CT and seven of them classified as true positives. CONCLUSIONS: Our results suggest that V/Q SPECT/CT is more sensitive and accurate than CTA when interpreted by general radiologists and nuclear medicine physicians.

Neuroimaging of Dopamine Transporter Density in the Striatum of Disordered Gamblers.

The aim of the present research was to add to the growing literature on dopamine and gambling disorder (GD) by assessing whether GD is associated with dopamine transporter (DAT) density in the ventral striatum compared to healthy controls and whether DAT density was associated with key characteristics of GD (e.g., abstinence, craving). In a cross-sectional investigation using single-photon emission computed tomography with a technetium-99m-labeled tropane derivative as a radiotracer with SPECT imaging, fifteen participants with GD and 15 controls (non-gambling individuals, matched for age, gender, handedness, and smoking status) were measured. The GD group completed self-reported questionnaires regarding gambling. Striatal DAT density did not differ between the two groups. Conversely, striatal DAT density correlated significantly with various measures of recent gambling, but not with measures of chronic gambling. Multivariate analysis, adjusted for age and smoking status, showed that DAT density in the left striatum correlated positively with time spent gambling and gambling craving in the last month, whereas DAT density in the right striatum correlated negatively with abstinence self-efficacy. The results suggests that DAT density in the striatum is associated with recent gambling activity and gambling expectation.

Disincronía miocárdica en pacientes sometidos a estudio de Spect gatillado y análisis de fase / Myocardial dyssynchrony in patients undergoing gated SPECT and phase analysis

Introducción: la perfusión miocárdica mediante SPECT gatillado (tomografía computarizada de emisión de fotón único) y análisis de fase permiten evaluar la disincronía mecánica y la fracción de eyección, indicando quienes podrían responder a la terapia de resincronización cardíaca. Objetivo: describir la frecuencia de disincronía miocárdica y su relación con los resultados del SPECT en el Hospital de San José de Bogotá entre mayo 2018 y febrero 2019. Metodología: estudio transversal en mayores de 18 años, con electrocardiograma de no más de 6 meses y SPECT gatillado. Para la información sociodemográfica, antecedentes cardíacos, parámetros de electrocardiograma y resultados del SPECT se empleó estadística descriptiva y análisis de correspondencias múltiples. Resultados: se incluyeron 539 pacientes con edad promedio de 68 años, 59.8% con sobrepeso y obesidad, 47.7% en clase funcional NYHA (New York Heart Association) III y IV, 48.4% fumadores y 26.9% diabéticos; 48.1% tenían cateterismo cardíaco y 45.3% infarto agudo de miocardio; en 31% la fracción de eyección del ventrículo izquierdo < 50%. La disincronía se determinó con un ancho de banda >135°; hubo disincronía en 202 pacientes (37.5%) que se relacionó con: género masculino, sobrepeso, diabetes, tabaquismo, infarto agudo del miocardio, colocación de stent, fracción de eyección del ventrículo izquierdo <40% o entre 40%-50% y dilatación isquémica transitoria (TID) >1.22 o entre 1.12-1.22. Discusión y conclusiones: el uso de la nueva herramienta del análisis de fase de medicina nuclear es factible y útil para determinar los pacientes respondedores a la terapia de resincronización cardíaca.

Introduction: Myocardial perfusion gated SPECT (simple photon emission computed tomography) with phase analysis allows the assessment of mechanical dyssynchrony and ejection fraction, for prediction of response to cardiac resynchronization therapy. Objective: to describe myocardial dyssynchrony frequency and its relationship with SPECT results at Hospital de San José de Bogotá between May 2018 and February 2019. Methodology: cross-sectional study in patients aged over 18 years, with a less than 6 months electrocardiogram and gated SPECT. Sociodemographic data, cardiovascular history, electrocardiogram parameters and SPECT results were evaluated using descriptive statistics and multiple correspondence analysis. Results: five-hundred-thirty-nine patients with a mean age of 68 years were included, 59.8% had overweight and obesity, 47.7% were NYHA (New York Heart Association) functional class III and IV, 48.4% smokers and 26.9% diabetics; 48.1% received cardiac catheterization and 45.3% had history of acute myocardial infarction; left ventricular ejection fraction was < 50% in 31%. Dyssynchrony was determined with a >135° bandwidth; dyssynchrony was evidenced in 202 patients (37.5%) and was related to male gender, overweight, diabetes, smoking, acute myocardial infarction, stent placement, left ventricular ejection fraction <40% or 40%-50% and transient ischemic dilation (TID) >1.22 or 1.12-1.22. Discussion and conclusions: the new nuclear medicine phase analysis tool is feasible and useful to identify cardiac resynchronization therapy responders.

Viabilidade do Implante de Eletrodo Ventricular Esquerdo na Terapia de Ressincronização Cardíaca Guiada por Gated SPECT e Remodelamento Ventricular / Feasibility of Left Ventricle Lead Implantation in Cardiac Resynchronization Therapy Guided by Gated SPECT and Ventricular Remodeling

Resumo Fundamento A terapia de ressincronização cardíaca (TRC) pode beneficiar pacientes com insuficiência cardíaca (IC) avançada. O índice de excentricidade anormal por gated SPECT está relacionado a alterações estruturais e funcionais do ventrículo esquerdo (VE). Objetivo O objetivo do presente estudo foi avaliar a viabilidade do implante de eletrodos do VE guiado por análise de fase e sua relação com o remodelamento ventricular. Métodos Dezoito pacientes com indicação de TRC foram submetidos à cintilografia miocárdica para orientar o implante, avaliando-se os parâmetros de excentricidade e forma ventricular. P < 0,05 foi adotado como significância estatística. Resultados Na linha de base do estudo, a maioria dos pacientes foi classificada como NYHA 3 (n = 12). Após a TRC, 11 dos 18 pacientes foram reclassificados para um menor grau de limitação funcional. Além disso, a qualidade de vida dos pacientes melhorou após a TRC. Foram observadas reduções significativas na duração do QRS, intervalo PR, índice de forma diastólica final, índice de forma sistólica final, volume sistólico e massa miocárdica pós-TRC. O eletrodo do VE da TRC foi posicionado concordante, adjacente e discordante em 11 (61,1%), 5 (27,8%) e 2 (11,1%) pacientes, respectivamente. A excentricidade sistólica e diastólica final demonstrou remodelamento reverso após a TRC. Conclusões O implante de eletrodo do VE em TRC guiado por cintilografia gated SPECT é viável. A colocação do eletrodo concordante ou adjacente ao último segmento a se contrair foi um determinante do remodelamento reverso.

Abstract Background Cardiac resynchronization therapy (CRT) may benefit patients with advanced heart failure (HF). Abnormal eccentricity index by gated SPECT is related to structural and functional alterations of the left ventricle (LV). Objective The aim of this study is to evaluate the feasibility of LV lead implantation guided by phase analysis and its relationship to ventricular remodeling. Methods Eighteen patients with indication for CRT underwent myocardial scintigraphy for implant orientation, and eccentricity and ventricular shape parameters were evaluated. P < 0.05 was adopted as statistical significance. Results At baseline, most patients were classified as NYHA 3 (n = 12). After CRT, 11 out of 18 patients were reclassified to a lower degree of functional limitation. In addition, patients' quality of life was improved post-CRT. Significant reductions were observed in QRS duration, PR interval, end-diastolic shape index, end-systolic shape index, stroke volume, and myocardial mass post-CRT. The CRT LV lead was positioned concordant, adjacent, and discordant in 11 (61.1%), 5 (27.8%), and 2 (11.1%) patients, respectively. End-systolic and end-diastolic eccentricity demonstrated reverse remodeling post-CRT. Conclusions LV lead implantation in CRT guided by gated SPECT scintigraphy is feasible. The placement of the electrode concordant or adjacent to the last segment to contract was a determinant of reverse remodeling.

Assessment of different regions of interest-based methods for [99mTc]Tc DAT-SPECT quantification using an anthropomorphic striatal phantom.

BACKGROUND AND AIMS: Molecular imaging of the dopamine transporters (DAT) provides valuable information about neurodegenerative diseases, such as Parkinson's. This study assessed the accuracy and precision of DAT-SPECT quantification methods. METHODS: Twenty-three DAT-SPECT images of a striatal phantom were acquired. The specific (caudate and putamen) and the non-specific (background activity) chambers were filled with [99mTc]Tc. Different specific-to-non-specific activity ratios (10, 9, 8, 7, 6, 5, 4, 3 and 2 to 1) and the specific binding ratio (SBR) were calculated. Five methods using ROIs were assessed: (a) Manual ROIs on SPECT images; (b) TwoBox and (c) ThreeBox methods and Volume of Interest (VOI) using structural images; (d) MRI and (e) CT. Accuracy was evaluated by the concordance correlation coefficient (CCC) and precision by Pearson's coefficient and linear regression. RESULTS: The SBR quantified in the specific and striatal chambers resulted in a CCC increase with a decrease in the nominal values. For lower SBR, MRI and CT showed higher CCCs when caudate ([Formula: see text] = 0.89 e [Formula: see text] = 0.84) and putamen ([Formula: see text] = 0.86 e [Formula: see text] = 0.82) were evaluated. For striatal assessments, the TwoBox method was the most accurate ([Formula: see text] = 0.95). High Pearson's coefficients were found in the correlations between all methods. CONCLUSIONS: All five methods showed high precision even when applied to images with different activities. MRI and CT were the most accurate for assessing the caudate or putamen. To assess the striatal chamber and in the absence of structural information, the TwoBox method is advisable.

Neurobiological substrates of chronic low back pain (CLBP): a brain [99mTc]Tc-ECD SPECT study.

BACKGROUND: Recent neuroimaging studies have demonstrated pathological mechanisms related to cerebral neuroplasticity in chronic low back pain (CLBP). Few studies have compared cerebral changes between patients with and without pain in the absence of an experimentally induced stimulus. We investigated the neurobiological substrates associated with chronic low back pain using [99mTc]Tc-ECD brain SPECT and correlated rCBF findings with the numeric rating scale (NRS) of pain and douleur neuropathique en 4 questions (DN4). Ten healthy control volunteers and fourteen patients with neuropathic CLBP due to lumbar disc herniation underwent cerebral SPECT scans. A quantitative comparison of rCBF findings between patients and controls was made using the Statistical Parametric Mapping (SPM), revealing clusters of voxels with a significant increase or decrease in rCBF. The intensity of CLBP was assessed by NRS and by DN4. RESULTS: The results demonstrated an rCBF increase in clusters A (occipital and posterior cingulate cortex) and B (right frontal) and a decrease in cluster C (superior parietal lobe and middle cingulate cortex). NRS scores were inversely and moderately correlated with the intensity of rCBF increase in cluster B, but not to rCBF changes in clusters A and C. DN4 scores did not correlate with rCBF changes in all three clusters. CONCLUSIONS: This study will be important for future therapeutic studies that aim to validate the association of rCBF findings with the pharmacokinetic and pharmacodynamic profiles of therapeutic challenges in pain.