SPECT Analysis Research Articles

An investigation of nano- and micron-sized carriers based on calcium carbonate and polylactic acid for oral administration of siRNA

ABSTRACT Background Oral delivery of small interfering RNAs (siRNAs) draws significant attention, but the gastrointestinal tract (GIT) has many biological barriers that limit the drugs’ bioavailability. The aim of this work was to investigate the potential of micro- and nano-sized CaCO3 and PLA carriers for oral delivery of siRNA and reveal a relationship between the physicochemical features of these carriers and their biodistribution. Research design and methods In vitro stability of carriers was investigated in simulated gastric and intestinal fluids. Toxicity and cellular uptake were investigated on Caco-2 cells. The biodistribution profiles of the developed CaCO3 and PLA carriers were examined using different visualization methods, including SPECT, fluorescence imaging, radiometry, and histological analysis. The delivery efficiency of siRNA loaded carriers was investigated both in vitro and in vivo. Results Micro-sized carriers were accumulated in the stomach and later localized in the colon tissues. The nanoscale particles (100–250 nm) were distributed in the colon tissues. nPLA was also detected in small intestine. The developed carriers can prevent siRNA from premature degradation in GIT media. Conclusion Our results reveal how the physicochemical properties of the particles, including their size and material type can affect their biodistribution profile and oral delivery of siRNA.

Definitive Diagnosis of Hepatic Hemangioma by 99mTc Labeled Red Blood Cell SPECT and Comparative Analysis with Ultrasound

Definitive Diagnosis of Hepatic Hemangioma by 99mTc Labeled Red Blood Cell SPECT and Comparative Analysis with Ultrasound

CT-guided spatial normalization of nuclear hybrid imaging adapted to enlarged ventricles: Impact on striatal uptake quantification

IntroductionSpatial normalization is a prerequisite step for the quantitative analysis of SPECT or PET brain images using volume-of-interest (VOI) template or voxel-based analysis. MRI-guided spatial normalization is the gold standard, but the wide use of PET/CT or SPECT/CT in routine clinical practice makes CT-guided spatial normalization a necessary alternative. Ventricular enlargement is observed with aging, and it hampers the spatial normalization of the lateral ventricles and striatal regions, limiting their analysis. The aim of the present study was to propose a robust spatial normalization method based on CT scans that takes into account features of the aging brain to reduce bias in the CT-guided striatal analysis of SPECT images. MethodsWe propose an enhanced CT-guided spatial normalization pipeline based on SPM12. Performance of the proposed pipeline was assessed on visually normal [123I]-FP-CIT SPECT/CT images. SPM12 default CT-guided spatial normalization was used as reference method. The metrics assessed were the overlap between the spatially normalized lateral ventricles and caudate/putamen VOIs, and the computation of caudate and putamen specific binding ratios (SBR). ResultsIn total 231 subjects (mean age ± SD = 61.9 ± 15.5 years) were included in the statistical analysis. The mean overlap between the spatially normalized lateral ventricles of subjects and the caudate VOI and the mean SBR of caudate were respectively 38.40 % (± SD = 19.48 %) of the VOI and 1.77 (± 0.79) when performing SPM12 default spatial normalization. The mean overlap decreased to 9.13 % (± SD = 1.41 %, P < 0.001) of the VOI and the SBR of caudate increased to 2.38 (± 0.51, P < 0.0001) when performing the proposed pipeline. Spatially normalized lateral ventricles did not overlap with putamen VOI using either method. The mean putamen SBR value derived from the proposed spatial normalization (2.75 ± 0.54) was not significantly different from that derived from the default SPM12 spatial normalization (2.83 ± 0.52, P > 0.05). ConclusionThe automatic CT-guided spatial normalization used herein led to a less biased spatial normalization of SPECT images, hence an improved semi-quantitative analysis. The proposed pipeline could be implemented in clinical routine to perform a more robust SBR computation using hybrid imaging.

Assessment of unilateral condylar hyperplasia with quantitative SPECT/CT

PurposeThe current study aimedto assess condylar activityin patients with unilateral condylar hyperplasia (UCH) with quantitative SPECT/CT. Patients and methodsThis retrospective study included patients with UCH who underwent quantitative SPECT/CT. SPECT analysis and quantification of SPECT/CT were performed, and the maximum count per pixel and SUVmax of either side of the condyles were calculated. Results39 patients were included in the analysisand classified into three subgroups according to the percentile differential right-left ratio: inactive group, left active (LA) group, and right active (RA) group. Totally, the SUVmax of the affected side is significantly higher than the unaffected side (active:5.93 ± 2.43 vs inactive:3.62 ± 1.76, P < 0.001), SUVmax-based ratios correlated well with the ratios based on maximum count (R = 0.944, P < 0.001). ROC analysis showed poorSUVmaxperformance in differentiation between theactive condyles and the inactive condyles due to the lower area under the curve (AUC) (0.588). In subgroup analysis, the affected side is significantly higher than the unaffected side in active groups with SUVmax, no significant difference was found between the active sides or the inactive sides of active groups. Interestingly, the SUVmax of the left side was statistically higher than that of the right sidein the inactive group (P = 0.01),while the left side of the right active group has significantlylower activitythan that in the inactive group, meanwhile,the right side showed no significant difference. Furthermore, each side showed no significant difference between the left active group and the inactive group. ConclusionsSUVmax is not an optimal measurement effectively used to evaluate active condyles. However, SUV ratios correlated well with the count ratios, and the left side of condyles showed a peculiar feature in condyle growth status reflected in radioactivity quantified with SPECT/CT, which needs further study to determine the role in the development of the UCH.

A - 128 Sex Differences in CBF in a Pediatric Sample of Depression: a SPECT Analysis.

The present study aims to determine whether there are differences in cerebral blood flow (CBF) levels in females versus males with depression. The data for this study was derived from an archival SPECT database. Participants in the female group (n = 140, Mage = 14.48) were like those in the male group (n = 241, Mage = 13.77). Multiple independent t-tests were performed between the female and male groups on the CBF levels in the left and right sides of the cerebellum, cingulum, frontal, occipital, parietal, and temporal lobes, and subcortical areas. CBF levels in males were higher than those of females in the following areas: the left and right sides of the cerebellum, and occipital lobe, the right side of the parietal lobe, and the temporal lobe. CBF levels in females were higher than those of males in the following areas: the left and right sides of the cingulum, the vermis, and the subcortical areas. While females had higher CBF in subcortical areas, the findings regarding higher CBF levels in males raise questions regarding prior literature which suggested that females have higher CBF than males in studies of depression subjects. These differences may be due to the differences in how males and females cope with depressive symptoms. Sex differences in CBF may suggest a contributing factor in the relationship between sex and responsiveness to antidepressant medication, ketamine treatment, and transcranial magnetic stimulation.

First-in-human study of a novel cell death tracer [99mTc]Tc-Duramycin: safety, biodistribution and radiation dosimetry in healthy volunteers

BackgroundImaging of cell death can provide an early indication of treatment response in cancer. [99mTc]Tc-Duramycin is a small-peptide SPECT tracer that recognizes both apoptotic and necrotic cells by binding to phosphatidylethanolamine present in the cell membrane. Preclinically, this tracer has shown to have favorable pharmacokinetics and selective tumor accumulation early after the onset of anticancer therapy. In this first-in-human study, we report the safety, biodistribution and internal radiation dosimetry of [99mTc]Tc-Duramycin in healthy human volunteers.ResultsSix healthy volunteers (3 males, 3 females) were injected intravenously with [99mTc]Tc-Duramycin (dose: 6 MBq/kg; 473 ± 36 MBq). [99mTc]Tc-Duramycin was well tolerated in all subjects, with no serious adverse events reported. Following injection, a 30-min dynamic planar imaging of the abdomen was performed, and whole-body (WB) planar scans were acquired at 1, 2, 3, 6 and 23 h post-injection (PI), with SPECT acquisitions after each WB scan and one low-dose CT after the first SPECT. In vivo 99mTc activities were determined from semi-quantitative analysis of the images, and time-activity curves were generated. Residence times were calculated from the dynamic and WB planar scans. The mean effective dose was 7.61 ± 0.75 µSv/MBq, with the kidneys receiving the highest absorbed dose (planar analysis: 43.82 ± 4.07 µGy/MBq, SPECT analysis: 19.72 ± 3.42 μGy/MBq), followed by liver and spleen. The median effective dose was 3.61 mSv (range, 2.85–4.14). The tracer cleared slowly from the blood (effective half-life of 2.0 ± 0.4 h) due to high plasma protein binding with < 5% free tracer 3 h PI. Excretion was almost exclusively renal.Conclusion[99mTc]Tc-Duramycin demonstrated acceptable dosimetry (< 5 mSv) and a favorable safety profile. Due to slow blood clearance, optimal target-to-background ratios are expected 5 h PI. These data support the further assessment of [99mTc]Tc-Duramycin for clinical treatment response evaluation.Trial registration: NCT05177640, Registered April 30, 2021, https://clinicaltrials.gov/study/NCT05177640.

FMR1 deletion in rats induces hyperactivity with no changes in striatal dopamine transporter availability

Autism Spectrum Disorder (ASD) is a pervasive neurodevelopmental disorder emerging in early life characterized by impairments in social interaction, poor verbal and non-verbal communication, and repetitive patterns of behaviors. Among the best-known genetic risk factors for ASD, there are mutations causing the loss of the Fragile X Messenger Ribonucleoprotein 1 (FMRP) leading to Fragile X syndrome (FXS), a common form of inherited intellectual disability and the leading monogenic cause of ASD. Being a pivotal regulator of motor activity, motivation, attention, and reward processing, dopaminergic neurotransmission has a key role in several neuropsychiatric disorders, including ASD. Fmr1Δexon 8 rats have been validated as a genetic model of ASD based on FMR1 deletion, and they are also a rat model of FXS. Here, we performed behavioral, biochemical and in vivo SPECT neuroimaging experiments to investigate whether Fmr1Δexon 8 rats display ASD-like repetitive behaviors associated with changes in striatal dopamine transporter (DAT) availability assessed through in vivo SPECT neuroimaging. At the behavioral level, Fmr1Δexon 8 rats displayed hyperactivity in the open field test in the absence of repetitive behaviors in the hole board test. However, these behavioral alterations were not associated with changes in striatal DAT availability as assessed by non-invasive in vivo SPECT and Western blot analyses.

Impaired neuronal integrity in traumatic brain injury detected by 123I-iomazenil single photon emission computed tomography and MRI

This study was aiming at investigating the extent of neuronal damage in cases of traumatic brain injury (TBI) with diffuse axonal injury (DAI) using 123I-iomazenil(IMZ) SPECT and MRI. We compared the findings in 31 patients with TBI without any major focal brain lesions and 25 age-matched normal controls. Subjects underwent 123I-IMZ SPECT and MRI, and also assessment by cognitive function tests. The partial volume effect of 123I-IMZ SPECT was corrected using MRI. In the patients with TBI, decreased spatial concentration of 123I-IMZ binding was detected in the medial frontal/orbitofrontal cortex, posterior cingulate gyrus, cuneus, precuneus, and superior region of the cerebellum. ROC analysis of 123I-IMZ SPECT for the detection of neuronal injury showed a high diagnostic ability of 123I-IMZ binding density for TBI in these areas. The decreased 123I-IMZ uptake density in the cuneus and precuneus was associated with cognitive decline after the injury. In the patients with TBI, brain atrophy was detected in the frontal lobe, anterior temporal and parietal cortex, corpus callosum, and posterior part of the cerebellum. Evaluation of the neuronal integrity by 123I-IMZ SPECT and MRI provides important information for the diagnosis and pathological interpretation in cases of TBI with DAI.

Nivolumab-DTPA-Based PD-1 Imaging Reveals Structural and Pathological Changes in Colorectal Carcinoma.

Programmed cell death protein 1 (PD-1) expression is considered a prognostic marker of tumor response to the immuno-blocking therapy. In this study, nivolumab was conjugated with diethylenetriamine pentaacetate (DTPA) via condensation reaction between amidogen and p-SCN-Bn-DTPA, which provided labeling sites for 99mTc4+ or Gd3+ ions. SPECT and magnetic resonance T1 weighted imaging (T1WI) analyses were performed on mouse models of colorectal carcinoma expressing humanized PD-1 antigen. Furthermore, PD-1 expression in intestinal tracks was assessed by immunohistochemistry, and then compared with the imageological findings. Nivolumab-DTPA was synthesized with varying molar ratios and was labeled with Gd or 99mTc with a chemical purity of 96.28 ± 1.16% and good stability. In SPECT images, lesions with high 99mTc-DTPA-nivolumab uptake and relatively clear background were shown at 6 h. Thereafter, the suspected intestinal thickening in Gd-free T1WI was observed at 2 h after the addition of Gd-DTPA-nivolumab. Notably, the results of both SPECT and T1WI analyses were consistent with the postmortem examination and immunohistochemistry results (for linear correlation with target to non-target ratios, R 2 = 0.8038, p < 0.05). In conclusion, nivolumab-DTPA could act as a probe precursor for identifying PD-1-positive lesions, not only through integrating the advantages of immunohistochemistry and molecular imaging but also by providing a noninvasive method for monitoring systemic changes.

99mTc-DPD myocardial uptake and regional longitudinal strain in aTTR amyloidosis cardiomyopathy

Abstract Funding Acknowledgements Type of funding sources: None. BACKGROUND amyloid cardiomyopathy is characterized by a typical "apical sparing" pattern of systolic longitudinal strain (LS) as visualized by echocardiography. Strain is well preserved at the apex of the left ventricle (LV) with a gradient from apex to base and the greatest impairment in the basal segments. The reason of this distribution is not clear. It could be a function of different amount of amyloid deposition. SPECT images using Technetium 99m bone tracers have shown a distribution mimicking regional LS. PURPOSE to compare regional myocardial LS and myocardial distribution of 99m Technetium-DPD (99m Tc-DPD) uptake in patients affected by aTTR amyloidosis cardiomyopathy. METHODS between 2016-2021 70 patients referred to our Cardiology Unit with heart failure/shortness of breath on exertion and showing significant left ventricular hypertrophy at 2-D echocardiography underwent 99m Tc-DPD scintigraphy to test the presence of cardiac amyloid. Grade 2-3 myocardial uptake at 180 minutes in the absence of abnormalities in the analysis of serum free light chains and serum and urine protein electrophoresis with immunofixation was considered sufficient for the diagnosis of aTTR amyloidosis. When scintigraphy was positive a SPECT study was performed to obtain semi quantitative measurements of segmental myocardial uptake (expressed as % of total myocardial uptake). Regional mean count was calculated by using a 6 basal, 12 mid and 2 apical segmental model. All patients underwent standard and 2D speckle tracking echocardiography. Mean systolic LS was calculated for each of 18 segments and mean basal (6 segments), mean mid (6 segments) and mean apical (6 segments) LS was calculated. RESULTS 46/70 patients had a positive scan and fulfilled criteria for aTTR amyloidosis. 33/46 had SPECT analysis. Male/female ratio was 29/4, age = 80 ± 6 years; 9/33 aortic stenosis; 19/33 carpal tunnel; 25/33 wild-type aTTR (4/33 ongoing genetic test); LV mass-=228 ± 48 g/m2; RWT = 0,73 ± 0,14; EF= 53 ± 9; EF to GLS ratio= 5,6 ±1,8. ANOVA showed a significant difference between basal, mid and apical strain as well as between basal, mid and apical uptake (-5,5 ± 4,4; -9,6 ± 3,2; -15,9 ± 5,6; p &amp;lt; 0,001; 55 ± 14; 62 ± 10; 51 ± 11; p = 0,0019). Comparison between groups showed that mean LS at the apex was significantly lower compared to basal and mid mean LS (Bonferroni test, p &amp;lt; 0,001) (Fig 1). Apical myocardial uptake was significantly lower compared to mid segment but not to basal (Bonferroni test, p = 0,02, p = 0,6 respectively) (Fig 1). Spearman’s test showed a correlation between LS and myocardial 99m Tc-DPD uptake (p = 0,01, Rho = 0,24). CONCLUSIONS Our data show that in this group of patients with cardiac aTTR amyloidosis apical LS is significantly lower compared to basal and mid segments and apical myocardial 99m Tc-DPD uptake is significantly lower compared to mid segments; a correlation between myocardial 99m Tc-DPD uptake distribution and the degree of LS impairment is present. Abstract Figure.

The Cingulate Island Sign is Useful for a Differential Diagnosis of Early-Onset Alzheimer's Disease and Dementia with Lewy Bodies: A 99mTc-ECD SPECT Study.

Early-onset dementia is fast-progressing compared with late-onset dementia, with major clinical characteristics including prominent focal cerebral symptoms. Given its economic and psychological implications, proper diagnosis and treatment at an early stage is essential. In the present study, the authors conducted a retrospective study to evaluate the usefulness of various numerical indices (including CIScore calculated by eZIS, cerebral blood flow SPECT analysis software) in the differential diagnosis of early-onset dementia. This study involved patients with early-onset and mild dementia who were receiving ambulatory care at our outpatient department specializing in Alzheimer's disease (14 MCI patients, 16 AD patients, and 16 probable/possible DLB patients). ROC analysis was performed for each SVA numerical index calculated by eZIS to calculate AUC. For the AD and DLB groups, correlation between the CIScore and MMSE was assessed. When SVA-A (severity) was used to differentiate AD from MCI and DLB from MCI, the respective AUC values were 0.960 and 0.911. When CIScore was used to differentiate AD from DLB (threshold value: 0.225), the obtained AUC value was 0.941, and the accuracy, sensitivity, and specificity were 90.6%, 87.5%, and 93.7%, respectively. No significant correlation was observed between the MMSE and CIScore scores in these disease groups. The results of this study have suggested that the SVA-A is a useful index for evaluating the conversion from MCI to either early-onset AD or DLB, and that the CIScore is useful for differentiating AD from DLB in both late-onset and early-onset dementia cases.

Myocardial ischemia and previous infarction contribute to left ventricular dyssynchrony in patients with coronary artery disease

AimsThe aim of this study was to characterize determinants of left ventricular mechanical dyssynchrony (LVMD) in patients with coronary artery disease (CAD). MethodsMedical records and results of myocardial perfusion SPECT/CT studies were evaluated in 326 patients with previously diagnosed CAD. LVMD was assessed with the phase analysis of ECG-gated myocardial SPECT. Dyssynchrony was described with phase histogram bandwidth (PHBW), standard deviation (PHSD) or entropy (PHE) values above limit of the highest normal. ResultsPrevalence of LVMD was 29% in CAD patients. Size of the infarction scar and ischemia extent correlated significantly with PHBW, PHSD and PHE (P < 0.001 for all). Independent predictors of LVMD were myocardial infarction scar (P = 0.004), ischemia extent (P = 0.003), and QRS duration (P = 0.003). Previous percutaneous coronary intervention and coronary artery bypass grafting did not independently predict dyssynchrony. ConclusionsAlmost one-third of CAD patients had significant LVMD. Dyssynchrony was associated with earlier myocardial infarction and presence of myocardial ischemia. Previous percutaneous coronary intervention and coronary artery bypass grafting did not independently predict dyssynchrony.

Uniformity of cardiac 123I-MIBG uptake on SPECT images in older adults with normal cognition and patients with dementia

IntroductionSome studies report that assessing regional 123I-cardiac MIBG uptake can aid in the diagnosis of Lewy body disease, but others report heterogeneity in healthy controls. We aimed to evaluate regional cardiac MIBG uptake patterns in healthy older adults and patients with dementia. Methods31 older adults with normal cognition, 15 Alzheimer’s disease (AD), and 17 Dementia with Lewy bodies (DLB) patients were recruited. 5 individuals had previous myocardial infarction. Participants with sufficient cardiac uptake for regional SPECT analysis (29/31 controls, 15/15 AD, 5/17 DLB) had relative uptake pattern recorded. Controls were assessed for risk of future cardiovascular events using QRISK2, a validated online tool. ResultsIn controls uptake was reduced in the inferior wall (85%), apex (23%), septum (15%), and lateral wall (8%). AD and DLB showed similar patterns to controls. Lung or liver interference was present in 61% of cases. Myocardial infarction cases showed regional reductions in uptake, but normal/borderline planar uptake. In controls, there was no relationship between cardiovascular risk score and uptake pattern. ConclusionsSignificant variability of regional cardiac 123I-MIBG uptake is common in cases with normal planar cardiac uptake. Heterogeneity of regional uptake appears non-specific and unlikely to aid in the diagnosis of Lewy body disease.

Predicting the Outcome of Epilepsy Surgery by Covariance Pattern Analysis of Ictal Perfusion SPECT.

Previous studies on the utility of specific perfusion patterns in ictal brain perfusion SPECT for predicting the outcome of temporal lobe epilepsy surgery used qualitative visual pattern classification, semiquantitative region-of-interest analysis, or conventional univariate voxel-based testing, which are limited by intra- and interrater variability or low sensitivity to capture functional interactions among brain regions. The present study performed covariance pattern analysis of ictal perfusion SPECT using the scaled subprofile model for unbiased identification of predictive covariance patterns. Methods: The study retrospectively included 18 responders to temporal lobe epilepsy surgery (Engel I-A at 12 mo follow-up) and 18 nonresponders (≥Engel I-B). Ictal SPECT images were analyzed with the scaled subprofile model masked to group membership for unbiased identification of the 16 covariance patterns explaining the highest proportion of variance in the whole dataset. Individual expression scores of the covariance patterns were evaluated for predicting seizure freedom after temporal lobe surgery by receiver-operating-characteristic analysis. Kaplan-Meier analysis including all available follow-up data (up to 60 mo after surgery) was also performed. Results: Among the 16 covariance patterns only 1 showed a different expression between responders and nonresponders (P = 0.03). This favorable ictal perfusion pattern resembled the typical ictal perfusion pattern in temporomesial epilepsy. The expression score of the pattern provided an area of 0.744 (95% CI, 0.577-0.911, P = 0.004) under the receiver-operating-characteristic curve. Kaplan-Meier analysis revealed a statistical trend toward longer seizure freedom in patients with positive expression score (P = 0.06). The median estimated seizure-free time was 48 mo in patients with positive expression score versus 6 mo in patients with negative expression score. Conclusion: The expression of the favorable ictal perfusion pattern identified by covariance analysis of ictal brain perfusion SPECT provides independent (from demographic and clinical variables) information for the prediction of seizure freedom after temporal lobe epilepsy surgery. The expression of this pattern is easily computed for new ictal SPECT images and, therefore, might be used to support the decision for or against temporal lobe surgery in clinical patient care.

Cardiac Sympathetic Activity and Rhythm Control Following Pulmonary Vein Isolation in Patients with Paroxysmal Atrial Fibrillation-A Prospective 123I-mIBG-SPECT/CT Imaging Study.

Background: Pulmonary vein isolation (PVI) and antiarrhythmic drug therapy are established treatment strategies to preserve sinus rhythm in atrial fibrillation (AF). However, the efficacy of both interventional and pharmaceutical therapy is still limited. Solid evidence suggests an important role of the cardiac sympathetic nervous system in AF. In this blinded, prospective observational study, we studied left ventricular cardiac sympathetic activity in patients treated with PVI and with antiarrhythmic drugs. Prospectively, Iodine-123-benzyl-guanidine single photon emission computer tomography (123I-mIBG-SPECT) was performed in a total of 23 patients with paroxysmal AF, who underwent PVI (n = 20) or received antiarrhythmic drug therapy only (n = 3), respectively. 123I-mIBG planar and SPECT/CT scans were performed before and 4 to 8 weeks after PVI (or initiation of drug therapy, respectively). For semiquantitative SPECT image analysis, attenuation-corrected early/late images were analyzed. Quantitative SPECT analysis was performed using the AHA 17-segment model of the left ventricle. Results: PVI with point-by-point radiofrequency ablation led to a significantly (p < 0.05) higher visual sympathetic innervation defect score when comparing pre-and post PVI. Newly emerging innervation deficits post PVI were localized predominantly in the inferior lateral wall. These findings were corroborated by semiquantitative SPECT analysis identifying inferolateral segments with a reduced tracer uptake in comparison to SPECT before PVI. Following PVI, patients with an AF relapse showed a different sympathetic innervation pattern compared to patients with sufficient rhythm control. Conclusions: PVI results in novel defects of cardiac sympathetic innervation. Differences in cardiac sympathetic innervation remodelling following PVI suggest an important role of the cardiac autonomous nervous system in the maintenance of sinus rhythm following PVI.

123I-Ioflupane SPECT and 18F-FDG PET Combined Use in the Characterization of Movement and Cognitive Associated Disorders in Neurodegenerative Diseases.

Both movement (MD) and cognitive (CD) disorders can occur associated in some neurodegenerative diseases, such as Parkinson's disease (PD) and Alzheimer's disease (AD). We further investigated the usefulness of 123I-Ioflupane SPECT and 18F-FDG PET combined use in patients with these disorders in the early stage. We retrospectively enrolled twenty-five consecutive patients with MD and CD clinical symptoms of recent appearance. All patients had undergone neurologic examination, neuropsychological tests, and magnetic resonance imaging. 123I-Ioflupane SPECT was performed in all cases, followed by 18F-FDG PET two weeks later. In the two procedures, both qualitative (QL) and quantitative (QN) image analyses were determined. In patients with both 123I-Ioflupane SPECT and 18F-FDG PET pathologic data, associated dopaminergic and cognitive impairments were confirmed in 56% of cases. Pathologic SPECT with normal PET in 16% of cases could diagnose MD and exclude an associated CD, despite clinical symptoms. On the contrary, normal SPECT with pathologic PET in 28% of cases could exclude basal ganglia damage while confirming CD. QN 123I-Ioflupane SPECT analysis showed better performance than QL since QN correctly characterized two cases of MD with normal QL. Moreover, correct classification of normal metabolism was made only by QN analysis of 18F-FDG PET in four cases, despite suspect areas of hypometabolism at QL. The combined use of these imaging procedures proved a reliable diagnostic tool to accurately identify and characterize MD and CD in early stage. QN analysis was effective in supporting QL evaluation, and its routine use is suggested, especially with inconclusive QL.

Analysis of brain perfusion single-photon emission tomography images using an easy Zscore imaging system for early diagnosis of Alzheimer's disease

To analyze single-photon emission tomography (SPECT) images of cerebral blood flow perfusion using an easy Z-score imaging system (eZIS) and explore the value of SPECT and eZIS in early diagnosis of Alzheimer's disease (AD). We retrospectively analyzed the clinical data of 71 subjects undergoing brain perfusion SPECT examination in our department from September, 2018 to September, 2020 and identified 31 eligible subjects for this study. Among these subjects, according to the NIA-AA criteria (2011 edition), 12 were diagnosed with mild cognitive impairment due to AD (MCI) and 11 with AD dementia stage (AD); 8 elderly subjects were healthy without cognitive impairment (NC). All these subjects underwent brain perfusion SPECT, and eZIS-assisted analysis was used to obtain the index values (severity, range and ratio). The differences in the severity, extent and ratio among the 3 groups were compared, and the diagnostic efficacy of single and joint analysis of the 3 indexes for early AD was analyzed. There was no significant difference in gender, age and education level among the 3 groups (P>0.05). Compared with those in NC group, the Mini Mental State Examination Scale (MMSE) scores were significantly lowered in AD group and MCI group; the MMSE score was significantly lower in AD group than in MCI group (P < 0.05). The patients with AD had significantly greater disease severity and extent than those with MCI group; the severity, range and ratio in both AD group and MCI group were significantly higher than those of NC group, but the ratio did not differ significantly between AD group and MCI group (P>0.05). In single index analysis, severity had the highest diagnostic performance (AUC=0.911) and sensitivity (87.0%); the diagnostic performance and sensitivity of joint analysis were better than those of single analysis, and joint analysis of range and ratio showed high diagnostic performance (AUC=0.948) and sensitivity (87.0%). The analysis of brain perfusion SPECT using an eZIS program can be useful for early diagnosis of AD.

Cardiac MRI viability study and its role in revascularization- Excerpts from a tertiary care cardiac centre

Abstract Funding Acknowledgements Type of funding sources: None. Background Assessment of cardiac viability based revascularization has not convincingly demonstrated, to improve patient outcomes statistically even by large trials like STITCH and PPAR-2 using SPECT and PET analysis. Here we used cardiac viability by cardiac MRI to guide us for revascularization and also found out problems arising in the statistical analysis for the same Methods It is a retrospective observational longitudinal follow up study whereby patients who had ischemic cardiomyopathy (confirmed with coronary angiogram) and who were admitted with features of heart failure or with acute coronary syndrome and who subsequently underwent cardiac MRI viability testing during the period from 1/02/2017 to 31/01/2020 were included. Patients were excluded who had non ischemic cardiomyopathy. Using cardiac MRI- LVEF, RVEF, Wall motion severity Index and Total viability percentage were additionally computed and analyzed. Patients were deemed having viable myocardium on ≤50% LGE in cardiac MRI and final treatment of CABG, PCI or only medical management was analyzed for the Primary end points of CV mortality, non-fatal CVA and non-fatal AMI Results Based on the criteria total of 94 patients were selected for the study, 53 patients kept on only medical management, 19 patients underwent PCI and 22 patients had CABG. The baseline characteristics of the study population were an average age of 60years, male (76%) with Diabetes Mellitus(69%) and Hypertension (41.5%) in them. Coronary Angiogram showed that 10.6% patients had LM involvement, 92% had LAD disease, 72% patients had LCX lesion and 74% had RCA disease. While average Echo LVEF was 35.82%, Cardiac MRI based mean LVEF was 30.78%. It was found that patients who were kept only on medical management had higher Wall motion Severity Index (2.05) over patients who were treated with PCI (1.94) or CABG (1.80) (p = 0.006). Also it was found that the Total viability percentage was less in patients kept only on medical management (74%) vs patients who were treated with PCI (78%) or CABG (77.8%)(p = 0.08) .It was found by cardiac MRI that patients with significant LAD lesions with viable LAD territory, those who underwent CABG or PCI based therapy had lesser mortality(7.69%,10%) over patients kept only on medical management (23%) (p = 0.407). Among patients with significant LAD lesions with non-viable LAD territory, those who underwent CABG or only medical management had lesser mortality (11.5%) than patients who underwent PCI (50%) (p = 0.137). Conclusion(s) Cardiac MRI based viability testing may guide the physician for optimal treatment but it does not reach statistical significance. The reasons maybe different arterial segments having different viability and anatomical hazards acting as cofounding factors. Viability being a continuum process does not follow a strict cut off of 50% LGE and 100% acute occluded vessel may not allow LGE.

Prognostic significance of cardiac 123I-MIBG SPECT imaging in patients with acute decompensated heart failure with preserved left ventricular ejection fraction

Abstract Background Cardiac sympathetic nerve dysfunction, which is assessed by I-123 metaiodobenzylguanidine (MIBG) imaging, is associated with the poor outcomes in patients with heart failure (HF). Most of the literature on the use of 123I-MIBG imaging is based on planar images in patients with chronic HF and reduced left ventricular ejection fraction (HFrEF), because It is technically challenging to conduct precise 123I-MIBG SPECT analysis in globally denervated heart, which is frequently observed in HFrEF patients. There was no information available on cardiac sympathetic nerve dysfunction evaluated by cardiac MIBG SPECT imaging in acute decompensated HF (ADHF) patients with preserved left ventricular ejection fraction (HFpEF). Purpose We aimed to clarify the prognostic significance of 123I-MIBG SPECT myocardial imaging in ADHF patients with HFpEF. Methods We enrolled 183 patients who were admitted for ADHF with HFpEF, discharged with survival. All patients underwent cardiac MIBG imaging at the timing of discharge. The cardiac MIBG heart to mediastinum ratio (H/M) was calculated on the early image and the delayed image (late H/M). We studied 156 patients after excluding 27 patients whose MIBG SPECT reconstruction was difficult due to too low MIBG uptake or extracardiac accumulation interference. SPECT analysis on the delayed image was conducted by using CardioBull, a fully automated software for the quantification of I-123 MIBG SPECT. All of 17 regional tracer uptake were compared with normal control database. A scoring algorithm for the evaluation of low uptake employs a 5-point scoring system as 0–4 for normal, mildly abnormal, moderately abnormal, severe abnormal, and perfusion defect, respectively. The summed severity (SSS) scores were obtained by summing the score for all segments. SSS could range from 0 to 68. The endpoint of this study is cardiac events defined as the composite of unplanned heart failure hospitalization and cardiac death. Results During a mean follow up period of 2.4±1.6 years, 60 patients reached cardiac events. SSS was significantly high in patients with than without cardiac events (20 [10–27] vs 7 [4–16], p&amp;lt;0.0001). SSS (p&amp;lt;0.0001) was significantly associated with cardiac events after multivariable Cox adjustment of age, sex, creatinine and log-transformed BNP level, although late H/M showed the significant association with the endpoint at the univariate Cox analysis. Kaplan-Meier analysis showed that patients with high SSS (&amp;gt;10, defined by median) had significantly greater risk of cardiac event (56% vs 21%, Hazard ratio: 3.56 (2.00–6.33, p&amp;lt;0.0001). ROC curve analysis showed that area under the curve (AUC) of SSS was 0.746 [95% CI:0.670, 0.812], which was significantly higher than that of late H/M (0.618 [95% CI:0.537, 0.695]) (p=0.0159). Conclusion Cardiac MIBG SPECT imaging was useful for risk stratification in ADHF patients with HFpEF. Funding Acknowledgement Type of funding source: None

Correlation between Global Longitudinal Strain and Ischemic Burden from Myocardial Perfusion Imaging in Multivessel Coronary Artery Disease Patients

Background: Global Longitudinal Strain (GLS) is a direct echocardiographic assessment of myocardial fiber deformation performed by speckle-tracking echocardiography that can better reflect ischemic and infarct areas and left ventricular function. Ischemic burden is a measurement of ischemic myocardium percentage and can be used to determine the management strategy of Multivessel Coronary Artery Disease (MVCAD). We aimed to investigate the value of GLS to predict the ischemic burden as detected by SPECT Myocardial Perfusion Imaging (MPI)&#x0D; Method: A cross-sectional study of patients with Multivessel Coronary Artery Disease who underwent Cardiac SPECT were included. GLS is assessed using the Automated Function Imaging (AFI) technique that is performed on the same day as the SPECT examination. Ischemic burden was measured by SPECT MPI using semi-quantitative scores on 17-segment assessment according to standard nomenclature and interpreted as small and moderate-large ischemic burden. &#x0D; Result: Total of 52 patients (40 males, mean age 56 ± 6.5 years). There was negative correlation with good strength between GLS value and ischemic burden (r = -0.706, P &lt; 0.001). Using ROC analysis, the optimal cut off value of GLS was &lt; (-13%) that yielded the highest sensitivity and specificity to discriminate between small and moderate-large ischemic burden. Sensitivity, specificity, positive and negative predictive value of GLS ≤(-13%) to predict moderate-large ischemic burden as detected by SPECT analysis were 80%, 75%, 67%, and 86%, respectively.&#x0D; Conclusion: A GLS value is a reliable parameter with good diagnostic value to predict small ischemic burden (&lt;10%) as detected by SPECT MPI. This parameter could also be applied to determine the management strategy of Multivessel Coronary Artery Disease (MVCAD) patients in daily practice.