Acid Scintigraphy Research Articles

Improvement of myocardial lipolysis in iodine-123-beta-methyl-P-iodophenyl-pentadecanoic acid scintigraphy in patients with idiopathic triglyceride deposit cardiomyovasculopathy treated with Tricaprin

Abstract Background Triglyceride deposit cardiomyovasculopathy (TGCV) is a rare intractable cardiovascular disorder (Orphanet ORPHAcode: 565612) in which defective intracellular lipolysis results in heart failure and coronary artery disease. Myocardial scintigraphy with iodine-123-β-methyl-P-iodophenyl-pentadecanoic acid (BMIPP) is useful for evaluating myocardial TG metabolism and its washout rate (WR) reflects myocardial lipolysis. A decreased WR (<10%) of BMIPP is one of the diagnostic criteria for TGCV. CNT-01, the active ingredient of which is tricaprin, a medium-chain triglyceride, has the potential to facilitate myocardial lipolysis in a mouse model. However, the effects of CNT-01 (tricaprin) on BMIPP scintigraphy in patients with TGCV remain unclear. Purpose To evaluate the effects of CNT-01 on BMIPP-WR in patients with TGCV. Methods An investigator-initiated, randomized, double-blind exploratory trial (Phase IIa) was conducted. Ten patients with idiopathic TGCV in our hospital were enrolled and orally administered 1.5 g/day of CNT-01 or placebo for 8 weeks. The endpoint was the delta WR on BMIPP scintigraphy. All the participants underwent BMIPP scintigraphy after overnight fasting. Following the protocol recommended by the Japanese Society of Nuclear Cardiology, 111 MBq of BMIPP was intravenously injected at rest after fasting for ≥ 12 h. Early and delayed images were obtained after 20 and 180–210 min, respectively. BMIPP scintigraphy at baseline and 8-week was performed using the same SPECT apparatus. WR is defined as the ratio of the difference between the counts in the early image and time-decay-corrected delayed image divided by the former. We used a recently proposed algorithm for calculating the WR based on the total count and analyzed the WRs (Ann Nucl Cardiol. 2023;9(1):19-25). Results A total of 5 patients were assigned to placebo and 5 patients were assigned to CNT-01. During the protocol, delta BMIPP-WRs were -6.18 ± 4.43 and 5.44 ± 2.57 % (95% confidence intervals, -12.33 to -0.03 and 1.88 to 9.00) in the placebo and CNT-01 groups, respectively. The baseline-adjusted difference in delta BMIPP-WR between the two groups was significant (p=0.005) (Picture). No significant changes were observed in clinical parameters. Conclusion This study demonstrated that CNT-01 improved myocardial lipolysis in patients with TGCV as measured by BMIPP scintigraphy.

Usefulness of visual classification for cardiac pathophysiology using count-washout rate map in iodine-123-beta-methyl-P-iodophenyl-pentadecanoic acid scintigraphy

Abstract Background Myocardial washout rate (WR) analysis of radiopharmaceuticals is utilized in nuclear cardiology to evaluate the clinical pathophysiology of the heart. WR is defined as the ratio of the difference between the counts in the early image and time-decay-corrected delayed image divided by the former. The myocardial WR of iodine-123-β-methyl iodophenyl-pentadecanoic acid (BMIPP) is an indicator of myocardial lipolysis, and a decreased WR (<10%) of BMIPP is one of the diagnostic criteria for triglyceride deposit cardiomyovasculopathy (TGCV). However, decreased BMIPP uptake in the early images, as in old myocardial infarction (OMI), would also cause a markedly decreased WR. Since the distinction between these clinical conditions cannot be made based on WR alone, simultaneous evaluation of the counts in the early image and WR is needed to properly understand the cardiac pathophysiology. Purpose To differentiate between TGCV and non-TGCV with OMI, both of which show decreased BMIPP WR, a new Count-WR Map (CWRM) method was evaluated. The purpose is to visually and easily distinguish between the two conditions using CWRM. Methods We introduced a CWRM consisting of two axes: counting in the early image, and WR. The count window was set to a maximum of the mean plus two standard deviations and a minimum of 50 counts, and the WR window was set to a maximum of 30 % and a minimum of -20%. CWRM was visually evaluated as normal, TGCV, non-TGCV with OMI, or TGCV with OMI. Results In normal cases, sufficient counts were observed in the early images, and WR did not decrease; CWRM showed light blue. In TGCV, sufficient counts were observed in the early image, but WRs markedly decreased; CWRM showed even orange. In non-TGCV with OMI, regions with decreased and preserved counts coexisted; CWRM showed light blue in the normal and black in the OMI region. In TGCV with OMI, CWRM showed orange in the TGCV myocardium and black in the OMI region (figure). Conclusions CWRM is useful for visually and easily differentiating TGCV from non-TGCV with OMI. CWRM can be applied to other cardiovascular diseases with count and WR variations for visual classification.

Congenital solitary functioning kidney: evaluations to do which, when, and how

Congenital solitary functioning kidney (CSFK) is characterized by an anatomical or functional absence of one kidney from birth. When suspected on perinatal ultrasonography (US), repeat US after birth should be performed for confirmation. Although postnatal 99mTc-dimercaptosuccinic acid scintigraphy (DMSA scan) is the gold standard for confirming CSFK, it carries the risk of radiation exposure; US alone is sufficient when performed by an experienced radiologist. One-third of patients with CSFK have additional congenital anomalies of the kidney and urinary tract at the solitary functioning kidney, the most common of which is vesicoureteral reflux. As evidence regarding vesicoureteral reflux with normal kidney US is correlated with significant urinary tract infection is lacking, voiding cystourethrogram may be considered in patients with CSFK with abnormal US findings. Furthermore, approximately 30% of patients with CSFK have extrarenal malformations. Moreover, up to 10% of them have syndromic features. In particular, examining for female genitalia malformations, which can have potential for complications from untreated obstructive malformations, is important. In conclusion, DMSA scan and voiding cystourethrogram are not necessary for all patients with CSFK, and the risk of each patient should be assessed to determine which test is needed during follow-up. The presence of extrarenal manifestations should also always be considered.

Renal Cortical Imaging with Tc-99m DMSA in Children: An Institutional Review.

Background Urinary tract infection (UTI) is one of the commonly encountered conditions in children. Dimercaptosuccinic acid (DMSA) scintigraphy is widely advocated for functional and morphological evaluation of the renal cortex including parenchymal defect. Moreover, only a small percentage of renal defects are detected by ultrasound. We aimed to examine DMSA scintigraphy of children and identify factors associated with cortical defect. Methods Patients aged ≤ 18 years old who underwent DMSA scintigraphy (November 18, 2019-February 2, 2023, 30 children) were included. All children received intravenous injections of 99m Tc-DMSA followed by static planar and single-photon-emission computed tomography imaging at 3 hours. Cortical findings and differential functions of the worst affected kidney were graded accordingly. Grade I has no more than two cortical defects, grade II has more than two cortical defects with normal parenchyma between the defects, while grade III is when generalized damage is noted, and grade IV is when a shrunken kidney is seen with no DMSA uptake. Normal functioning kidney is when the relative function at 45 to 55%, mildly reduced function at 40 to 44%, and substantially impaired function at 10 to 39%, while nonfunctioning is when the differential split renal function < 10%. All data were then statistically analyzed. Results Majority was female (53%). The mean age was 5.85 years. UTI episodes were 73%. Twenty-two children had congenital urinary tract anomalies. All patients with vesicoureteric refluxes (VURs) had positive defects. Scintigraphy showed abnormalities in 17 children affecting unilateral (64%) or both kidneys (36%). There were 17 children (57%) respectively in the abnormal DMSA scan findings category with normal until significant impairment of the functioning kidney category. VURs were significantly associated with abnormal scintigraphy ( p < 0.05). A significant association was found between abnormal DMSA scan findings and differential renal function ( p < 0.05). Conclusion Significant association was noted between VURs and abnormal DMSA scintigraphy, abnormal DMSA scan findings, and impaired differential renal function. Special consideration should be given to these cases.

99mTc-DMSA and 99mTc-DTPA identified renal dysfunction due to microplastic polyethylene in murine model

In the previous study (Im et al., 2022), we revealed microplastic (MP) was accumulated and cleared through the kidneys via PET imaging. Here, we aimed to identify the renal dysfunction due to polyethylene (PE) MP in the kidney tissue. Mice were exposed to 100 ppm (∼equivalent to 0.1 mg/mL)/100 μL of PE for 12 weeks (n = 10). PE uptake in the kidney tissues was confirmed using confocal microscopy. QuantSeq analysis was performed to determine gene expression. Renal function assessment was performed using 99mTc-Diethylene triamine penta acetic acid or 99mTc-Dimercaptosuccinic acid. Measurement of creatinine, BUN, and albumin levels in serum and urine samples was also estimated. [18F]-FDG was also acquired. PE increased expression of Myc, CD44, Programmed Death-Ligand 1 (PD-L1), and Hypoxia-Inducible Factor (HIF)-1α, which indicates a potential link to an increased risk of early-onset cancer. An increase in glucose metabolism of [18F]-FDG were observed. We assessed renal failure using 99mTc-Diethylene triamine penta acetic acid and 99mTc-Dimercaptosuccinic acid scintigraphy to determine the renal function. Renal failure was confirmed using serum and urine creatinine, serum blood urea nitrogen levels, serum albumin levels, and urine albumin levels in PE exposed mice, relative to the control. In sum, PE exposure induced renal dysfunction in a murine model.

Effect of access sheath diameter used in percutaneous nephrolithotomy on renal function: a prospective randomized study.

We aimed to determine the effect of the access sheath diameter used in percutaneous nephrolithotomy (PNL) on renal function. We also investigated the predictors of impaired renal function. Data were prospectively collected from patients who underwent PNL from December 2020 to December 2021. The patients were randomized into two groups according to access sheath diameter: Group 1 (22 Fr, n = 44) and Group 2 (28 Fr, n = 44). Relative renal function (RRF) was calculated by technetium-99m dimercaptosuccinic acid scintigraphy, and glomerular filtration rate (GFR) was calculated by diethylenetriamine pentaacetic acid scintigraphy. A difference of 5% or more in RRF was considered a significant functional change. Preoperative and postoperative Kidney Injury Molecule-1 (KIM-1) levels were measured. Preoperative demographic data and stone characteristics were similar between the groups. There were also no statistically significant differences between the groups in terms of scar development, changes in RRF, GFR, or KIM-1/creatinine (Cr) (p > 0.05). Significant deterioration in RRF was detected in a total of six (6.8%) patients, three in each group. The factors predicting loss of function were analyzed by regrouping the patients without loss of function as Group A (n = 82) and those with loss as Group B (n = 6). Only stone volume was statistically significant in multivariate analysis (p = 0.002). Access sheath diameter had no significant effect on renal function after PNL. However, the stone volume was found to independently correlate to a loss of renal function after PNL.

Regional Distribution of Extracellular Volume Quantified by Cardiac CT in Aortic Stenosis: Insights Into Disease Mechanisms and Impact on Outcomes.

Extracellular volume fraction (ECV) is a marker for myocardial fibrosis and infiltration, can be quantified using cardiac computed tomography (ECVCT), and has prognostic utility in several diseases. This study aims to map out regional differences in ECVCT to obtain greater insights into the pathophysiological mechanisms of ECV expansion and its clinical implications. Three prospective cohorts were included: patients with aortic stenosis (AS) and coexisting AS and transthyretin cardiac amyloidosis were referred for a transcatheter aortic valve replacement and had ECG-gated CT angiography and Technetium-99m-labelled 3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy to differentiate between the 2 cohorts. Controls had CT angiography and cardiac magnetic resonance demonstrating no significant coronary artery disease or infarction. Global and regional ECVCT was analyzed, and its association with mortality was assessed for patients with AS. In 199 patients, controls (n=65; 66% male), AS (n=115), and coexisting AS and transthyretin cardiac amyloidosis (n=19) had a global ECVCT of 26.1 (25.0-27.8%) versus 29.1 (27.5-31.1%) versus 37.4 (32.5-46.6%), respectively; P<0.001. Across cohorts, ECVCT was higher at the base (versus apex), the inferoseptum (versus anterolateral wall), and the subendocardium (versus subepicardium); P<0.05 for all. Among patients with AS, epicardial ECVCT, rather than any other regional value or global ECVCT, was the strongest predictor of mortality at a median of 3.9 (max 6.3) years (adjusted hazard ratio, 1.21 [95% CI, 1.08-1.36]; P=0.002). Regional differences in ECVCT suggest a predilection for fibrosis and amyloid infiltration at the base, subendocardium, inferior wall, and septum more than the anterior and lateral myocardium. ECVCT can predict long-term mortality with the subepicardium demonstrating the strongest discriminatory power. URL: https://www.clinicaltrials.gov; Unique identifiers: NCT03029026 and NCT03094143.

Impact of iodine contrast media on gamma camera-based GFR and factors affecting the difference between serum creatinine-based estimated GFR and Gate's GFR.

We aimed to elucidate the factors underlying the difference between estimated glomerular filtration rate (eGFR) calculated from serum creatinine and Gate's GFR (gGFR) measured using technetium-99m diethylene triamine pentaacetic acid ( 99m Tc-DTPA) scintigraphy. This study was based on consecutive patients who underwent 99m Tc-DTPA scintigraphy at our hospital between January 2021 and December 2022 and whose blood serum creatinine data were obtained on the same day as the 99m Tc-DTPA scintigraphy. Relationships between the ratio of gGFR and eGFR (gGFR/eGFR) and age, sex, BMI, visceral fat, psoas muscle index (PMI), serum blood urea nitrogen, and creatinine level were investigated based on 75 patients. Additionally, for 44 patients who had two or more follow-up DTPA studies, we compared gGFR values for studies that used iodine contrast media (ICM) for computed tomography before same-day 99m Tc-DTPA studies and those that did not in the same patients. Weak correlations were observed between gGFR/eGFR and PMI ( r = 0.30), BMI ( r = 0.24), and the visceral fat area ( r = 0.33). Multi-regression analyses showed that gGFR/eGFR was correlated with PMI ( β = 0.34, P < 0.01) and approached significance with the visceral fat area ( β = 0.24, P = 0.05). A significant difference was observed in gGFR between patients who received ICM before the 99m Tc-DTPA renogram and those who did not ( P < 0.001, eGFR 80.5 ± 19.0 vs. 91.7 ± 27.8 ml/min). ICM administration temporarily decreased gGFR, and increased muscle mass increased the difference between eGFR and gGFR values.

Potential Effects of Ischemic Postconditioning and Changes in Heat Shock Protein 72 in Patients with Acute Myocardial Infarction without Prodromal Angina.

The effectiveness of ischemic postconditioning (iPoC) in patients with ST-elevation myocardial infarction (STEMI) without ischemic preconditioning has not been determined. Therefore, we investigated the impact of iPoC and its potential mechanism related to heat shock protein 72 (HSP72) induction on myocardial salvage in patients with STEMI without prodromal angina (PA).We retrospectively analyzed data from 102 patients with STEMI with successful reperfusion among 323 consecutive patients with acute coronary syndrome. Among these, 55 patients with iPoC (iPoC (+) ) underwent 4 cycles of 60-second inflation and 30-second deflation of the angioplasty balloon. Both the iPoC (+) and iPoC (-) groups were divided into 2 further subgroups: patients with PA (PA (+) ) and those without (PA (-) ). We analyzed HSP72 levels in neutrophils, which were measured until 48 hours after reperfusion. I-123 β-methyl-p-iodophenyl-pentadecanoic acid (BMIPP) scintigraphy was performed within a week of reperfusion therapy. In 64% of patients, thallium-201 (TL) scintigraphy was performed 6-8 months after STEMI onset.Using BMIPP and TL, in the PA (-) subgroups, the iPoC (+) group had a significantly greater myocardial salvage ratio than the iPoC (-) group. iPoC was identified as an independent predictor of the myocardial salvage ratio. The HSP72 increase ratio was significantly elevated in the iPoC (+) PA (-) group. Importantly, the myocardial salvage effect in patients without PA was significantly correlated with the HSP72 increase ratio, which was greater in patients with iPoC.These results suggest the potential impact of iPoC via HSP72 induction on myocardial salvage; however, the effects may be limited to patients with STEMI without PA.

Deep learning-based attenuation correction method in 99mTc-GSA SPECT/CT hepatic imaging: a phantom study.

This study aimed to evaluate a deep learning-based attenuation correction (AC) method to generate pseudo-computed tomography (CT) images from non-AC single-photon emission computed tomography images (SPECTNC) for AC in 99mTc-galactosyl human albumin diethylenetriamine pentaacetic acid (GSA) scintigraphy and to reduce patient dosage. A cycle-consistent generative network (CycleGAN) model was used to generate pseudo-CT images. The training datasets comprised approximately 850 liver phantom images obtained from SPECTNC and real CT images. The training datasets were then input to CycleGAN, and pseudo-CT images were output. SPECT images with real-time CT attenuation correction (SPECTCTAC) and pseudo-CT attenuation correction (SPECTGAN) were acquired. The difference in liver volume between real CT and pseudo-CT images was evaluated. Total counts and uniformity were then used to evaluate the effects of AC. Additionally, the similarity coefficients of SPECTCTAC and SPECTGAN were assessed using a structural similarity (SSIM) index. The pseudo-CT images produced a lower liver volume than the real CT images. SPECTCTAC exhibited a higher total count than SPECTNC and SPECTGAN, which were approximately 60% and 7% lower, respectively. The uniformities of SPECTCTAC and SPECTGAN were better than those of SPECTNC. The mean SSIM value for SPECTCTAC and SPECTGAN was 0.97. We proposed a deep learning-based AC approach to generate pseudo-CT images from SPECTNC images in 99mTc-GSA scintigraphy. SPECTGAN with AC using pseudo-CT images was similar to SPECTCTAC, demonstrating the possibility of SPECT/CT examination with reduced exposure to radiation.

Coronary artery disease in cardiac amyloidosis

Abstract Background Cardiac amyloidosis is an important disease causing significant morbidity and mortality. Due to the ageing society as well as better diagnostic tools such as 3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy (DPD scan), cardiac amyloidosis has increased in prevalence, however, the coexistence, as well as the differences in presentation with coronary artery disease (CAD), has not yet been discovered. Purpose The purpose of the study is to evaluate the prevalence of CAD in patients with cardiac amyloidosis, to assess differences in late gadolinium enhancement (LGE) in cardiac MRI, and to assess differences in symptoms such as dyspnea. Materials and Methods We retrospectively assessed all patients with cardiac amyloidosis at our center and screened for an evaluation of coronary artery disease with coronary angiography, coronary CT, or myocardial scintigraphy. In all patients, who underwent cardiac MRI we assessed the pattern of LGE using the cardiac left ventricular segmentation model published by the AHA [1]. Results 295 patients (27% female, 74 ± 11 years) with cardiac amyloidosis (26% AL-amyloidosis, 74% ATTR-amyloidosis) were retrospectively assessed. Of those, 205 (69%) had a CAD evaluation. In 69 patients (34%), significant CAD was present, 10 patients (5%) had undergone CABG and 48 patients (23%) had received a PCI in the past. In patients with CAD, 3 patients (4%) suffered from NYHA IV and 51 patients (74%) were symptomatic with NYHA II or NYHA III. There were no significant differences to patients without CAD (p=0.252). In 153 patients (75%), cardiac MRI was performed. In 7% of the patients, no LGE was obvious, in 84%, a diffuse circular subendocardial to transmural LGE with basoapical gradient, typical for cardiac amyloidosis, could be observed. In 6% of the cases, a subendocardial pattern typical for post-ischemic changes could be observed; in 56% of the patients, a previous myocardial infarction was known. In the remaining 3%, LGE in the insertion points could be observed. Conclusion With 34%, CAD is highly prevalent in patients with cardiac amyloidosis. In 28%, a coronary intervention (surgical or interventional) was performed, making coronary interventions in patients with cardiac amyloidosis a feasible option. Cardiac MRI in patients with concomitant CAD and cardiac amyloidosis often shows the typical diffuse LGE, therefore, visualization of postischemic changes in these patients is difficult. Furthermore, symptoms do not differ between patients with CAD and no CAD.

Monitoring patisiran and inotersen treatment with quantitative SPECT/CT in hereditary transthyretin amyloid cardiomyopathy

Abstract Background Novel ribonucleic acid interference (RNAi) therapeutics such as patisiran and inotersen have been shown to benefit neurologic disease course and quality of life in patients with hereditary transthyretin amyloidosis (ATTRv). Purpose We aimed to determine treatment effects on myocardial amyloid load determined by quantitative single photon emission computed tomography/computed tomography (SPECT/CT) in patients with ATTRv-related cardiomyopathy (ATTRv-CM) and to identify nuclear imaging biomarkers to quantify and monitor response to therapy. Methods ATTRv-CM patients underwent [99mTc]-radiolabeled diphosphono-1,2-propanodicarboxylic acid ([99mTc]-DPD) scintigraphy and SPECT/CT imaging before and after 12 months of treatment with patisiran (n=5) or inotersen (n=4). Results Patisiran-treated patients had a significant reduction in cardiac uptake as measured by standardized uptake values (SUVpeak: 7.98 g/mL ±0.87 vs. 6.50 g/mL ±1.59, p=0.025, Figure 1A; SUVmax: 8.80 g/mL ±0.94 vs. 6.96 g/mL ±1.59, p=0.009, Figure 1B; SUVmean: 5.64 g/mL ±1.01 vs. 4.42 g/mL ±1.26, p=0.016, Figure 1C). Patients treated with inotersen showed evidence of stabilization in cardiac SUV uptake (SUVpeak: 8.56 g/mL ±2.25 vs. 7.99 g/mL ±1.90, p=0.665; SUVmax: 9.29 g/mL ±2.39 vs. 8.79 g/mL ±2.03, p=0.719; SUVmean: 5.07 g/mL ±1.46 vs. 4.86 g/mL ±0.95, p=0.834) but had significant deterioration in left ventricular (LV) function (LV cardiac index: 3.39 L/min/m2 ±0.04 vs. 2.94 L/min/m2 ±0.01, p=0.028, Figure 1D). Comparison of cardiac SUV uptake and longitudinal cardiac function revealed significant correlations between longitudinal changes in cardiac SUVpeak and LV global longitudinal strain (r=-0.658, p=0.027, Figure 1E) and right ventricular free wall longitudinal strain (r=-0.771, p=0.008, Figure 1F). Conclusions In conclusion, using serial quantitative SPECT/CT imaging, we demonstrated that patisiran treatment significantly reduces cardiac SUV uptake in ATTRv-CM patients, indicating regression of cardiac TTR amyloid. Our data suggest that quantitative SPECT/CT imaging may be a valid tool to quantify and monitor response to disease-specific RNAi therapeutic agents in ATTRv-CM patients.Figure 1Graphical Abstract

Novel SPECT/CT biomarker in transthyretin cardiac amyloidosis: correlation with myocardial amyloid load and cardiac structure and function

Abstract Background Single photon emission computed tomography/computed tomography (SPECT/CT) with determination of standardized uptake value (SUV) allows quantification of cardiac amyloid deposition. Purpose We aimed to investigate the relationship between quantitative cardiac tracer uptake determined by SPECT/CT and myocardial amyloid load, as well as cardiac structure and function in patients with transthyretin amyloid cardiomyopathy (ATTR-CM), and to identify nuclear imaging biomarkers for monitoring disease progression. Methods ATTR-CM patients underwent [99mTc]-radiolabeled diphosphono-1,2-propanodicarboxylic acid ([99mTc]-DPD) scintigraphy and SPECT/CT imaging (n=40) with determination of SUV, as well as cardiac magnetic resonance imaging (CMR, n=25) and transthoracic echocardiography (TTE, n=40). Results We observed significant correlations (r, Pearson's correlation coefficient) between SUV retention index and myocardial amyloid load [CMR extracellular volume (ECV): r=0.565, p=0.004, Figure 1A], cardiac structure [CMR interventricular septum: r=0.409, p=0.042, Figure 1B; CMR left ventricular mass index: r=0.508, p=0.010, Figure 1C], longitudinal cardiac function [TTE left ventricular global longitudinal strain (LV GLS): r=0.531, p=0.003, Figure 1D; TTE right ventricular free wall longitudinal strain: r=0.470, p=0.024, Figure 1E; TTE left atrial reservoir strain (LASr): r=-0.434, p=0.038, Figure 1F] and cardiac biomarkers [N-terminal prohormone of brain natriuretic peptide (NT-proBNP): r=0.475, p=0.004; high-sensitive troponin T (hs-TnT): r=0.358, p=0.027]. ATTR-CM patients were divided into two cohorts based on the median (4.32 mg/dL) of SUV retention index (low SUV uptake cohort: ≤4.32 mg/dL, n=20; high SUV uptake cohort: &amp;gt;4.32 mg/dL, n=20). We observed significant between-cohort differences with respect to LV ejection fraction (low SUV uptake: 51.8% vs. high SUV uptake: 46.2%, p=0.045), LV GLS (-14.5% vs. -11.1%, p=0.001), LASr (11.6% vs. 7.1%, p=0.023), NT-proBNP (1300 pg/mL vs. 2786 pg/mL, p&amp;lt;0.001), hs-TnT (42.9 ng/L vs. 62.2 ng/L, p=0.016) and 6-min walk distance (440.1 m vs. 330.1 m, p=0.022). Conclusions Using quantitative SPECT/CT imaging, we demonstrated that SUV retention index correlates with myocardial amyloid load, cardiac structure and function, and cardiac biomarkers. Our data suggest that quantitative SPECT/CT imaging with determination of SUV retention index may be a valid tool to monitor disease progression in ATTR-CM patients.Figure 1

Impact of increased DPD scintigraphy on timing of diagnosis and prognosis of transthyretin cardiac amyloidosis over the course of ten years

Abstract Background 99mTechnetium labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) scintigraphy is a sensitive non-invasive method for imaging transthyretin cardiac amyloidosis (ATTR-CA). The emergence of novel pharmacotherapies for ATTR-CA has resulted in much greater disease awareness. Objective We aimed to assess the level of increased demand for DPD scintigraphy and its influence on the clinical phenotype of patients diagnosed with ATTR-CA over the past 10 years. Methods This was a retrospective observational cohort study of patients referred to our centre (2012–2022) for DPD scintigraphy in whom ATTR-CA was a differential diagnosis. The protocol consisted of a planar whole-body acquisition performed at 3 hours after the injection, followed by single-photon emission computed tomography imaging of the thorax. Intensity of myocardial uptake on the planar 99mTc-DPD scan was categorized as 0 to 3 according to the Perugini grading system. A diagnosis of ATTR-CA was established on the basis of heart failure symptoms together with characteristic echocardiography or cardiac magnetic resonance imaging, and a grade 2 or 3 cardiac uptake on Tc99m-DPD in the absence of biochemical evidence of a monoclonal dyscrasia. Results As of December 2022, we identified 426 DPD scans performed in 421 patients (mean age 75 ± 12 yr, 72% male) referred for 99mTc-DPD, of whom 151 subsequently had a diagnosis of ATTR-CA confirmed. Patients diagnosed with AL-CA (n=2) were excluded for the purpose of this analysis. The number of DPD scans increased significantly in 2021-2022 (211 out of 426 studies) compared with previous 2 year periods (p&amp;lt;0.01) with an increasing proportion of referrals in this period made by cardiologists (p&amp;lt;0.05). In patients diagnosed with ATTR-CA, the proportion of grade 2 versus grade 3 Perugini scans increased in 2021-2022 compared with earlier years. There was no difference in survival among patients according to DPD grading (Figure 1; log rank p = 0.35). There was also no difference in survival between patients with ATTR-CA patients and DPD negative patients presenting with other forms of restrictive cardiomyopathy (Figure 2; HR 1.46, 95%CI [0.94-2.26], log rank p= 0.09). Conclusions Based on DPD grading, patients are being referred earlier by cardiologists with suspected ATTR-CA. DPD grading does not, however, carry prognostic significance in those patients subsequently diagnosed with ATTR-CA. Patients referred but who are not subsequently diagnosed with ATTR-CA have a similarly adverse prognosis to those with ATTR-CA; this forgotten cohort of non-specific restrictive cardiomyopathy is worthy of further follow up and investigation.5 year survival for all patients

Voiding Sistoüretrogram ile Tanı Konulan Vezikoüreteral Reflü'nün Saptanmasında Dinamik Böbrek Sintigrafisinin Rolü

Aims: This study aims to evaluate the role of standardized dynamic renal scintigraphy (DRS) in recognizing vesicoureteral reflux (VUR) in patients detected with VUR by voiding cystourethrography (VCUG). Methods: The data of all pediatric patients who underwent both VCUG and DRS [technetium-99m diethylenetriamine pentaacetic acid (Tc-99m DTPA) or technetium-99m mercaptoacetyltriglycine dynamic renal scintigraphy (Tc-99m MAG-3)] in our hospital between 2013 and 2022 were retrospectively reviewed. Tc-99m MAG-3 was used in infants and Tc-99m DTPA radiopharmaceutical in children over one year old. According to VCUG findings, VUR grades were grouped as grade I-II-III low-grade VUR and IV-V high-grade VUR. The role of DRS in detecting VUR in both low and high-VUR-grade groups was evaluated. Results: A total of 56 patients (and 69 renal units), 23 girls (%41.1), and 33 boys (%68.9) were included in this study. The median value of the time elapsed between the DRS and VCUG examinations was nine days. According to VCUG, VUR was grade I in five renal units, grade II in 19 renal units, grade III in six renal units, grade IV in six renal units, and grade V in 33 renal units. DRS detected VUR in two of 30 renal units (%6.7) in the low VUR grade group. On the other hand, VUR was observed with DRS in 27 of 39 renal units (%69.2) in the high VUR grade group. Conclusions: Standardized DRS shows very low sensitivity in recognizing low-grade VUR, and its performance in detecting high-grade VUR is comparatively better. Raising awareness among clinicians that VUR can be observed with standardized DRS will benefit the patient in terms of early detection of accompanying VUR pathologies.

Reduction in 99mTc-DPD myocardial uptake with therapy of ATTR cardiomyopathy

Aims: Novel ribonucleic acid interference (RNAi) therapeutics such as patisiran and inotersen have been shown to benefit neurologic disease course and quality of life in patients with hereditary transthyretin amyloidosis (ATTRv). We aimed to determine the impact of RNAi therapeutics on myocardial amyloid load using quantitative single photon emission computed tomography/computed tomography (SPECT/CT) imaging in patients with ATTRv-related cardiomyopathy (ATTRv-CM). We furthermore compared them with wild-type ATTR-CM (ATTRwt-CM) patients treated with tafamidis. Methods and results: ATTRv-CM patients underwent [99mTc]-radiolabeled diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) scintigraphy and quantitative SPECT/CT imaging before and after 12 months (IQR: 11.0–12.0) of treatment with RNAi therapeutics (patisiran: n = 5, inotersen: n = 4). RNAi treatment significantly reduced quantitative myocardial uptake as measured by standardised uptake value (SUV) retention index (baseline: 5.09 g/mL vs. follow-up: 3.19 g/mL, p = .028) in ATTRv-CM patients without significant improvement in cardiac function. Tafamidis treatment resulted in a significant reduction in SUV retention index (4.96 g/mL vs. 3.27 g/mL, p < .001) in ATTRwt-CM patients (historical control cohort: n = 40) at follow-up [9.0 months (IQR: 7.0–10.0)] without beneficial impact on cardiac function. Conclusions: RNAi therapeutics significantly reduce quantitative myocardial uptake in ATTRv-CM patients, comparable to tafamidis treatment in ATTRwt-CM patients, without impact on cardiac function. Serial 99mTc-DPD SPECT/CT imaging may be a valuable tool to quantify and monitor response to disease-specific therapies in both ATTRv-CM and ATTRwt-CM.

Diagnostic and prognostic contribution of DPD scintigraphy in transthyretin V30M cardiac amyloidosis

Background Early diagnosis and prognostic stratification of cardiac transthyretin amyloidosis are crucial. Although 99mTc 3,3-diphosphono-1,2-propanedicarboxylic acid (DPD) scintigraphy is the preferred method for the non-invasive diagnosis, its accuracy appears to be limited in transthyretin amyloidosis protein (ATTR) V30M mutation. Furthermore, its prognostic value in this mutation is unknown. This study investigated the diagnostic value of DPD scintigraphy to detect ATTR cardiomyopathy in V30M mutation and explored its prognostic value regarding mortality. Methods A total of 288 ATTR V30M mutation carriers (median age: 46 years; 49% males) without myocardial thickening (defined as septal thickness ≥13mm) attributable to other causes and who underwent DPD scintigraphy were enrolled. ATTR cardiomyopathy was defined by septal thickness ≥13mm and at least one of the criteria: late heart-to-mediastinum (H/M) 123I-metaiodobenzylguanidine (MIBG) uptake ratio <1.60; electrical heart disease or biopsy-documented amyloidosis. Results ATTR cardiomyopathy was identified in 41 (14.2%) patients and cardiac DPD uptake in 34 (11.8%). During a mean follow-up of 33.6 ± 1.2 months, 16 patients died (5.6%). Mortality was 14 times higher in patients with ATTR cardiomyopathy, 13 times higher in those with DPD uptake and 10 times higher in those with late H/M MIBG <1.60. The combined assessment of septal thickness and cardiac DPD uptake improved risk stratification: patients without septal thickening and without DPD retention had an excellent prognosis while those who presented either or both of them had a significantly worse prognosis, with 5-year mortality rates ranging from 39.9 to 53.3%. Conclusions DPD scintigraphy is useful for prognostic stratification of ATTR V30M mutation carriers. Patients without septal thickening and no DPD uptake present the best prognosis compared to those with any signs of cardiac involvement.

Usefulness of preset count acquisition in pediatric 99m Tc-DMSA planar imaging.

This study was aimed at determining the minimum acquisition count to provide diagnosable image quality (DIQ) and investigating the usefulness of preset count acquisition (PCA) for planar images of pediatric 99mTc-dimercaptosuccinic acid (DMSA) scintigraphy. First, we calculated a coefficient of variation (CV) for DIQ with the shortest acquisition time through visual evaluation in 12 pediatric patients who underwent 99mTc-DMSA scintigraphy. Second, a minimum acquisition count to achieve the CV for DIQ was determined with the single regression analysis using CV as an explanatory variable and the total acquisition count as an objective variable in 81 pediatric patients. Finally, we compared PCA images based on the minimum acquisition count and preset time acquisition (PTA) images for 5min in terms of the acquisition time, CV, and renal uptake ratio in another 23 pediatric patients. The visual evaluation showed that the CV corresponding to DIQ with the shortest acquisition time was 27.1%. The total acquisition count corresponding to DIQ was revealed to be 299,764 in the single regression analysis and was determined to be 300,000 after rounding. The CV and its standard deviation in PCA at 300,000 counts and PTA for 5min were 26.4 ± 0.6% and 24.8 ± 1.3%, respectively. The standard deviation of CV in PCA at 300,000 counts was smaller than that in PTA for 5min, indicating little variation in image quality between cases. The acquisition time in PCA at 300,000 counts (3.1 ± 0.7min) was shorter than that in PTA for 5min (5.0 ± 0.0min). The intraclass correlation coefficient between renal uptake ratios for PCA and PTA was 0.98, indicating an extremely high concordance. The minimum acquisition count required for the DIQ was 300,000. In addition, PCA at 300,000 counts was demonstrated to be useful by providing stable image quality at the shortest acquisition time.

Regression of Myocardial 99mTc-DPD Uptake After Tafamidis Treatment of Cardiac Transthyretin Amyloidosis.

Cardiac transthyretin amyloidosis is an infiltrative cardiomyopathy with high mortality. To date, there are no specific biomarkers to directly assess disease activity and response to specific treatments. Our aim was to evaluate scintigraphic changes after treatment with the transthyretin stabilizer tafamidis. Methods: We included patients who had undergone 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) scintigraphy before tafamidis initiation and after at least 9 mo. Tracer activity was assessed visually and quantitatively as SUVmax Results: The study included 14 patients who were on tafamidis for 44 ± 14 mo. We observed regression of Perugini grade in 5 patients, unchanged grade in 9 patients, and regression of mean heart-to-contralateral-lung ratio (P = 0.015) and SUVmax (P = 0.005). There were no changes in N-terminal pro-B-type natriuretic peptide or echocardiographic measures. Conclusion: Treatment with tafamidis results in regression of myocardial 99mTc-DPD uptake. 99mTc-DPD scintigraphy may provide useful imaging biomarkers to assess response to treatment.

Acquisition time reduction in pediatric 99mTc‐DMSA planar imaging using deep learning

Given the potential risk of motion artifacts, acquisition time reduction is desirable in pediatric 99m Tc-dimercaptosuccinic acid (DMSA) scintigraphy. The aim of this study was to evaluate the performance of predicted full-acquisition-time images from short-acquisition-time pediatric 99m Tc-DMSA planar images with only 1/5th acquisition time using deep learning in terms of image quality and quantitative renal uptake measurement accuracy. One hundred and fifty-five cases that underwent pediatric 99m Tc-DMSA planar imaging as dynamic data for 10min were retrospectively collected for the development of three deep learning models (DnCNN, Win5RB, and ResUnet), and the generation of full-time images from short-time images. We used the normalized mean squared error (NMSE), peak signal-to-noise ratio (PSNR), and structural similarity index metrics (SSIM) to evaluate the accuracy of the predicted full-time images. In addition, the renal uptake of 99m Tc-DMSA was calculated, and the difference in renal uptake from the reference full-time images was assessed using scatter plots with Pearson correlation and Bland-Altman plots. The predicted full-time images from the deep learning models showed a significant improvement in image quality compared to the short-time images with respect to the reference full-time images. In particular, the predicted full-time images obtained by ResUnet showed the lowest NMSE (0.4 [0.4-0.5] %) and the highest PSNR (55.4 [54.7-56.1] dB) and SSIM (0.997 [0.995-0.997]). For renal uptake, an extremely high correlation was achieved in all short-time and three predicted full-time images (R2 >0.999 for all). The Bland-Altman plots showed the lowest bias (-0.10) of renal uptake in ResUnet, while short-time images showed the lowest variance (95% confidence interval: -0.14, 0.45) of renal uptake. Our proposed method is capable of producing images that are comparable to the original full-acquisition-time images, allowing for a reduction of acquisition time/injected dose in pediatric 99m Tc-DMSA planar imaging.