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Accurate quantification of plaque imaging using 18F-NaF PET requires partial volume correction (PVC). PVC of PET data was implemented by the use of a local projection (LP) method. LP-based PVC was evaluated with an image quality (NEMA) and with a thorax phantom with “plaque-type” lesions of 18-36 mL. The validated PVC method was then applied to a cohort of 17 patients, each with at least one plaque in the carotid or ascending aortic arteries. In total, 51 calcified (HU > 110) and 16 non-calcified plaque lesions (HU < 110) were analyzed. The lesion-to-background ratio (LBR) and the relative change of LBR (ΔLBR) were measured on PET. Following PVC, LBR of the spheres (NEMA phantom) was within 10% of the original values. LBR of the thoracic lesions increased by 155% to 440% when the LP-PVC method was applied to the PET images. In patients, PVC increased the LBR in both calcified [mean = 78% (−8% to 227%)] and non-calcified plaques [mean = 41%, (−9%-104%)]. PVC helps to improve LBR of plaque-type lesions in both phantom studies and clinical patients. Better results were obtained when the PVC method was applied to images reconstructed with point spread function modeling.

The diagnosis of coronary microvascular disease (CMVD) remains challenging. Perfusion PET-derived myocardial blood flow (MBF) reserve (MBFR) can quantify CMVD but is not widely available. Thrombolysis in Myocardial Infarction (TIMI) frame count (TFC) is an angiography-based method that has been proposed as a measure of CMVD. Here, we compare TFC and PET-derived MBF measurements to establish the role of TFC in assessing for CMVD. We use coronary modeling to elucidate the relationship between MBFR and TFC and propose TFC thresholds for identifying CMVD. In a cohort of 123 individuals (age 58 ± 12.1, 63% women, 41% Caucasian) without obstructive coronary artery disease who had undergone perfusion PET and coronary angiography for clinical indications, we compared TFC and perfusion PET parameters using Pearson correlation (PCC) and linear regression modeling. We used mathematical modeling of the coronary circulation to understand the relationship between these parameters and performed Receiver Operating Curve (ROC) analysis. We found a significant negative correlation between TFC and MBFR. Sex, race and ethnicity, and nitroglycerin administration impact this relationship. Coronary modeling showed an uncoupling between TFC and flow in epicardial vessels. In ROC analysis, TFC performed well in women (AUC 0.84-0.89) and a moderately in men (AUC 0.68-0.78). We established an inverse relationship between TFC and PET-derived MBFR, which is affected by patient selection and procedural factors. TFC represents a measure of the volume of the epicardial coronary compartment, which is increased in patients with CMVD, and performs well in identifying women with CMVD.

Reducing levels of mitochondrial iron by diet or pharmacological chelation ameliorates symptoms of cigarette smoke–induced chronic obstructive pulmonary disease in mice. Chronic obstructive pulmonary disease (COPD) is linked to both cigarette smoking and genetic determinants. We have previously identified iron-responsive element–binding protein 2 ( IRP2 ) as an important COPD susceptibility gene and have shown that IRP2 protein is increased in the lungs of individuals with COPD. Here we demonstrate that mice deficient in Irp2 were protected from cigarette smoke (CS)-induced experimental COPD. By integrating RNA immunoprecipitation followed by sequencing (RIP-seq), RNA sequencing (RNA-seq), and gene expression and functional enrichment clustering analysis, we identified Irp2 as a regulator of mitochondrial function in the lungs of mice. Irp2 increased mitochondrial iron loading and levels of cytochrome c oxidase (COX), which led to mitochondrial dysfunction and subsequent experimental COPD. Frataxin-deficient mice, which had higher mitochondrial iron loading, showed impaired airway mucociliary clearance (MCC) and higher pulmonary inflammation at baseline, whereas mice deficient in the synthesis of cytochrome c oxidase, which have reduced COX, were protected from CS-induced pulmonary inflammation and impairment of MCC. Mice treated with a mitochondrial iron chelator or mice fed a low-iron diet were protected from CS-induced COPD. Mitochondrial iron chelation also alleviated CS-induced impairment of MCC, CS-induced pulmonary inflammation and CS-associated lung injury in mice with established COPD, suggesting a critical functional role and potential therapeutic intervention for the mitochondrial-iron axis in COPD.

Purpose Cardiac amyloidosis, a restrictive heart disease with high mortality and morbidity, is underdiagnosed due to limited targeted diagnostic imaging. The primary aim of this study was to evaluate the utility of 18 F-florbetapir for imaging cardiac amyloidosis. Methods We performed a pilot study of cardiac 18 F-florbetapir PET in 14 subjects: 5 control subjects without amyloidosis and 9 subjects with documented cardiac amyloidosis. Standardized uptake values (SUV) of 18 F-florbetapir in the left ventricular (LV) myocardium, blood pool, liver, and vertebral bone were determined. A 18 F-florbetapir retention index (RI) was computed. Mean LV myocardial SUVs, target-to-background ratio (TBR, myocardial/blood pool SUV ratio) and myocardial-to-liver SUV ratio between 0 and 30 min were calculated. Results Left and right ventricular myocardial uptake of 18 F-florbetapir were noted in all the amyloid subjects and in none of the control subjects. The RI, TBR, LV myocardial SUV and LV myocardial to liver SUV ratio were all significantly higher in the amyloidosis subjects than in the control subjects (RI median 0.043 min −1 , IQR 0.034 – 0.051 min −1 , vs. 0.023 min −1 , IQR 0.015 – 0.025 min −1 , P  = 0.002; TBR 1.84, 1.64 – 2.50, vs. 1.26, IQR 0.91 – 1.36, P  = 0.001; LV myocardial SUV 3.84, IQR 1.87 – 5.65, vs. 1.35, IQR 1.17 – 2.28, P  = 0.029; ratio of LV myocardial to liver SUV 0.67, IQR 0.44 – 1.64, vs. 0.18, IQR 0.15 – 0.35, P  = 0.004). The myocardial RI, TBR and myocardial to liver SUV ratio also distinguished the control subjects from subjects with transthyretin and those with light chain amyloid. Conclusion 18 F-Florbetapir PET may be a promising technique to image light chain and transthyretin cardiac amyloidosis. Its role in diagnosing amyloid in other organ systems and in assessing response to therapy needs to be further studied.

The field of nuclear cardiology is witnessing growing interest in the use of cardiac PET for the evaluation of patients with coronary artery disease (CAD). The available evidence suggests that myocardial perfusion PET provides an accurate means for diagnosing obstructive CAD, which appears superior to SPECT especially in the obese and in those undergoing pharmacologic stress. The ability to record changes in left ventricular function from rest to peak stress and to quantify myocardial perfusion (in mL/min/g of tissue) provides an added advantage over SPECT for evaluating multivessel CAD. There is growing and consistent evidence that gated myocardial perfusion PET also provides clinically useful risk stratification. Although the introduction of hybrid PET/CT technology offers the exciting possibility of assessing the extent of anatomic CAD (CT coronary angiography) and its functional consequences (ischemic burden) in the same setting, there are technical challenges in the implementation of CT-based transmission imaging for attenuation correction. Nonetheless, this integrated platform for assessing anatomy and biology offers a great potential for translating advances in molecularly targeted imaging into humans.

Recent technological advances in myocardial perfusion imaging may warrant the use of lower injected activity. We evaluated whether quantitative measures of stress myocardial perfusion defects using Tc-99m sestamibi and low-energy high-resolution (LEHR) collimators are equivalent to lower dose SPECT-CT with cardiac multifocal collimators and software (IQ·SPECT). 93 patients underwent one-day rest-stress gated SPECT-CT. Following conventional rest imaging, 925-1100 MBq (25-30 mCi) of Tc-99m sestamibi was injected during stress testing. Stress SPECT-CT images were acquired two ways: with LEHR (13 minutes) and IQ·SPECT (7 minutes). Low-dose IQ·SPECT stress was simulated by subsampling the full-dose data to half-, quarter-, and eighth-count levels. Abnormalities were quantified using the total perfusion deficit (TPD) score and dose-specific databases. The mean ± SD of the differences between LEHR and IQ·SPECT TPD scores were −1.01 ± 5.36%, −0.10 ± 5.81%, 1.78 ± 4.81%, and 1.75 ± 6.05% at full, half, quarter, and eighth doses, respectively. Differences were statistically significant for quarter and eighth doses. Correlation between LEHR and IQ·SPECT was excellent at all doses (R ≥ 0.93). Bland-Altman plots demonstrated minimal bias. With IQ·SPECT, quantitative stress SPECT-CT imaging is possible with half of the standard injected activity in half the time. Los recientes avances tecnológicos en la imagen de perfusión miocárdica (MPI) pueden justificar el uso de una menor actividad inyectada. Nosotros evaluamos si las mediciones cuantitativas de los defectos de perfusión en estrés usando Tc-99m sestamibi y colimadores de baja energía y alta resolución (LEHR) son equivalentes a dosis menores en SPECT-CT con colimadores multifocales y programa de procesamiento cardiacos (IQ·SPECT). 93 pacientes sometidos a gated SPECT-CT reposo – estrés en un solo día. Después de la imagen convencional de reposo, se inyectaron 925-1100 MBq (25-30 mCi) de Tc-99m sestamibi durante la prueba de estrés. Las imágenes de estrés con SPECT-CT se adquirieron de dos formas: con LEHR (13 min) y con IQ·SPECT (7 min). La dosis baja con IQ·SPECT fue simulada haciendo un submuestreo de los datos de la dosis completa a niveles de la mitad, la cuarta y la octava parte de las cuentas. Las anormalidades se cuantificaron usando el déficit total de perfusión (TPD) y bases de datos específicas por dosis. Las medias ± DE de las diferencias de los valores de TPD entre LEHR y IQ·SPECT fueron −1.01 ± 5.36%, −0.10 ± 5.81%, 1.78 ± 4.81% y 1.75 ± 6.05% a dosis completa, media, cuarta y octava parte, respectivamente. Las diferencias fueron estadísticamente significativas para la cuarta y octava parte de dosis. La correlación entre LEHR con IQ·SPECT fue excelente con todas la dosis (R > 0.93). Las gráficas de Bland-Altman demostraron mínimo sesgo. Con IQ·SPECT, el estrés cuantitativo mediante la imagen de SPECT-CT es posible realizarlo con la mitad de la actividad estándar inyectada y en la mitad de tiempo. 最近心脏灌注显像(MPI)的技术进步使得在较低注射剂量的条件下MPI成像变得可行。 本文评估:采用Tc-99m甲氧基异丁基异腈显影剂和低能量高分辨率准直器定量测定负荷状态下心肌血流灌注缺损(LEHR方法), 是否等效于采用心脏多焦点准直器和软件进行的较低剂量SPECT-CT的测定结果 (IQ·SPECT方法)。 对入选的93个病人均采用负荷一日法/静息门控SPECT-CT 显影方案。 按照常规的方法进行静息图像的采集后, 在运动过程中静脉注射 925-1100 MBq(25-30mCi) 的 Tc-99m (甲氧基异丁基异腈)。 负荷SPECT-CT 图像是以两种方式采集:13分钟的LEHR和7分钟的 IQ·SPECT。 低剂量的负荷 IQ·SPECT是用全剂量样本的子样本来模拟, 分别是半剂量、 四分之一剂量和八分之一剂量。 用血流灌注缺损总积分(TPD)和剂量特征化数据库对心肌灌注异常进行定量。 分别采用LEHR与IQ·SPECT方法时, TPD积分差值的平均值±标准方差是 −1.01 ±5.36%, −0.10 ± 5.81%, 1.78 ± 4.81% 和 1.75 ± 6.05%, 分别对应于全剂量、半剂量、 四分之一剂量和八分之一剂量。在四分之一和八分之一剂量时采用LEHR与IQ·SPECT方法测定的TPD差值在统计学上有显著性差异。在所有剂量段时采用LEHR与 IQ·SPECT 方法测定的TPD都有很好的相关性(R ≥ 0.93)。Bland-Altman图形表明了最小偏差。 采用IQ·SPECT方法, 将图像采集时间和显影剂注射剂量都减半应用于负荷SPECT-CT成像是可行的。

Purpose We have investigated a new technology for fabricating phantoms with fine details for use in small-animal imaging. Procedures We used a high-resolution, 3-D stereolithography (SL) system to produce performance-evaluation phantoms such as cold-rod Derenzo, hot-channel Derenzo, and Defrise phantoms. SL performance was estimated by measuring the dimensions of many structures using a microscope. We also evaluated the degree of water absorption by two different SL resins, Somos® 11120 and Accura® 40, after curing. Results The average bias and precision of the cold-rod structures over the size range 0.5 to 1.0 mm, were −0.4% and 1.74%, respectively. The water absorption study showed that Somos® 11120 is a more suitable material for nuclear medicine applications. Conclusion We have demonstrated that SL is a robust and accurate method for fabrication of phantoms for small-animal imaging systems.

We investigated the impact of the quantitation and reconstruction protocol on clinical tasks. The performance of standard clinical reconstruction procedures in discrimination tasks related to the diagnosis of prodromal Alzheimer's disease (AD) was compared with the performance of a quantitative approach incorporating improved corrections for scatter, attenuation, intrinsic spatial resolution, and distance-dependent spatial resolution. Seventeen normal controls (normal group), 56 subjects who did not have dementia, who did have memory problems, but who did not develop AD within 5 y of follow-up (questionable group), and 27 subjects who did not have dementia, who did have memory problems, and who did develop AD over the follow-up period (converter group) were considered in this study. (99m)Tc-hexamethylpropyleneamine oxime SPECT and MRI studies were performed for each subject at baseline. The standard quantitation protocol (STD), routinely used in our clinic, consisted of Compton window scatter correction followed by filtered backprojection with attenuation correction using a uniform attenuation map. In the improved quantitative approach (QUAN), projections were corrected for scatter by use of a general spectral method and reconstructed by use of ordered-subset(s) expectation maximization, incorporating corrections for collimator response and attenuation using both a uniform attenuation map (QUANunif) and a nonuniform attenuation map (QUANnonunif). Mean SPECT activity concentration and MRI volume were estimated for 7 structures: rostral anterior cingulate gyrus, caudal anterior cingulate gyrus, posterior cingulate gyrus, hippocampus, basal forebrain, amygdala, and the banks of the superior temporal sulcus. Data were analyzed by pairwise discriminant analysis, and performance in binary group discrimination was measured by correlated receiver-operating-characteristic analysis. The use of QUANnonunif yielded a small but systematic improvement in discrimination accuracy for normal versus converter groups (accuracy or area under the receiver-operating-characteristic curve [Az], 0.965), normal versus questionable groups (Az, 0.973), and questionable versus converter groups (Az, 0.881) compared with the results obtained with QUANunif (Az, 0.955, 0.962, and 0.866, respectively). Discrimination performance was significantly lower (P < 0.05) with STD than with QUAN in all 3 tasks (Az with STD, 0.906, 0.878, and 0.768, respectively). MRI volume estimation led to a lower overall performance in all 3 tasks than did QUANnonunif (Az with MRI, 0.947, 0.917, and 0.872, respectively). Improved quantitative image reconstruction with accurate compensation for scatter, attenuation, and variable collimator response led to significantly better performance in discrimination tasks related to the diagnosis of prodromal AD than did standard clinical reconstruction procedures. The use of a nonuniform brain attenuation map yields a small improvement in discrimination accuracy.