Imaging with [99mTc]HMPAO – a novel perspective: investigation of [99mTc]HMPAO leg muscle uptake in metabolic diseases

Background Sensitive imaging modalities in the diagnosis of microcircular complications of the lower extremities induced by metabolic diseases are becoming a focus of interest. Purpose To investigate the [99mTc]HMPAO uptake of the legs in type 2 diabetes mellitus (T2DM) and obesity, and to search for associations with clinical parameters and nerve conducting studies. Material and Methods A total of 57 patients with controlled T2DM and 46 obese participants without DM were enrolled in the study. [99mTc]HMPAO SPECT/CT examinations were performed to evaluate the radiopharmaceutical accumulation of the legs. For the quantitative assessment of tracer uptake, standardized uptake value (SUVpeak) was measured in fixed spheric volumes of interest placed on both sural muscles on the attenuation-corrected images. Measurement of current perception threshold applying Neurometer (NM-01/CPT) was used to evaluate peripheral nerve dysfunction. Laboratory parameters assessing the glucose homeostasis of the study participants were also measured. Results In the diabetic group, significantly lower leg SUV values were detected compared to the non-DM obese group (median: 0.517 vs. 0.607; P < 0.001). Body mass index (BMI) ( P < 0.0001), age ( P = 0.0283), HbA1c ( P = 0.0068), and glucose level ( P = 0.0044) proved to be significant predictors of muscle tracer uptake. Neurometer studies showed positive correlation with HbA1c levels in the T2DM group ( P = 0.0002). Conclusion We assume that [99mTc]HMPAO uptake of leg muscles is associated with microcirculation, so quantitative [99mTc]HMPAO SPECT/CT might be a sensitive method for evaluating lower limb microvascular alterations. BMI, age, HbA1c, and glucose level may be significant predictors of peripheral vascular abnormalities triggered by metabolic disturbances.

Spatial covariance analysis of FDG-PET and HMPAO-SPECT for the differential diagnosis of dementia with Lewy bodies and Alzheimer's disease.

We investigated diagnostic characteristics of spatial covariance analysis (SCA) of FDG-PET and HMPAO-SPECT scans in the differential diagnosis of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD), in comparison with visual ratings and region of interest (ROI) analysis. Sixty-seven patients (DLB 29, AD 38) had both HMPAO-SPECT and FDG-PET scans. Spatial covariance patterns were used to separate AD and DLB in an initial derivation group (DLB n=15, AD n=19), before being forward applied to an independent group (DLB n=14, AD n=19). Visual ratings were by consensus, with ROI analysis utilising medial occipital/medial temporal uptake ratios. SCA of HMPAO-SPECT performed poorly (AUC 0.59 +/- 0.10), whilst SCA of FDG-PET (AUC 0.83 +/- 0.07) was significantly better. For FDG-PET, SCA showed similar diagnostic performance to ROI analysis (AUC 0.84 +/- 0.08) and visual rating (AUC 0.82 +/- 0.08). In contrast to ROI analysis, there was little concordance between SCA and visual ratings of FDG-PET scans. We conclude that SCA of FDG-PET outperforms that of HMPAO-SPECT and performed similarly to other analytical approaches, with the potential to improve with larger derivation groups. Compared to visual rating, SCA of FDG-PET relies on different sources of group variance to separate DLB from AD.

The Diagnostic Value of 99mTc-HMPAO-Labelled White Blood Cell Scintigraphy and 18F-FDG PET/CT in Cardiac Device-Related Infective Endocarditis—A Systematic Review

(1) Background: Treatment of cardiac arrhythmias and conduction disorders with the implantation of a cardiac implantable electronic device (CIED) may lead to complications. Cardiac device-related infective endocarditis (CDRIE) stands out as being one of the most challenging in terms of its diagnosis and management. Developing molecular imaging modalities may provide additional insights into CDRIE diagnosis. (2) Methods: We performed a systematic literature review to critically appraise the evidence for the diagnostic performance of the following hybrid techniques: single photon emission tomography with technetium99m-hexamethylpropyleneamine oxime–labeled autologous leukocytes (99mTc-HMPAO-SPECT/CT) and positron emission tomography with fluorodeoxyglucose (18F-FDG PET/CT). An analysis was performed in accordance with PRISMA and GRADE criteria and included articles from PubMed, Embase and Cochrane databases. (3) Results: Initially, there were 2131 records identified which had been published between 1971–2021. Finally, 18 studies were included presenting original data on the diagnostic value of 99mTc-HMPAO-SPECT/CT or 18F-FDG PET/CT in CDRIE. Analysis showed that these molecular imaging modalities provide high diagnostic accuracy and their inclusion in diagnostic criteria improves CDRIE work-up. (4) Conclusions: 99mTc-HMPAO-SPECT/CT and 18F-FDG PET/CT provide high diagnostic value in the identification of patients at risk of CDRIE and should be considered for inclusion in the CDRIE diagnostic process.

99mTc-HMPAO SPECT imaging reveals brain hypoperfusion during status epilepticus

Status epilepticus (SE) is a clinical emergency with high mortality. SE can trigger neuronal death or injury and alteration of neuronal networks resulting in long-term cognitive decline or epilepsy. Among the multiple factors contributing to this damage, imbalance between oxygen and glucose requirements and brain perfusion during SE has been proposed. Herein, we aimed to quantify by neuroimaging the spatiotemporal course of brain perfusion during and after lithium-pilocarpine-induced SE in rats. To this purpose, animals underwent 99mTc-HMPAO SPECT imaging at different time points during and after SE using a small animal SPECT/CT system. 99mTc-HMPAO regional uptake was normalized to the injected dose. In addition, voxel-based statistical parametric mapping was performed. SPECT imaging showed an increase of cortical perfusion before clinical seizure activity onset followed by regional hypo-perfusion starting with the first convulsive seizure and during SE. Twenty-four hours after SE, brain 99mTc-HMPAO uptake was widely decreased. Finally, chronic epileptic animals showed regionally decreased perfusion affecting hippocampus and cortical sub-regions. Despite elevated energy and oxygen requirements, brain hypo-perfusion is present during SE. Our results suggest that insufficient compensation of required blood flow might contribute to neuronal damage and neuroinflammation, and ultimately to chronic epilepsy generated by SE.

Effects of cranioplasty in cerebral blood perfusion using quantification with 99mTc-HMPAO SPECT-CT

PURPOSE: SSFS is an underdiagnosed complication of craniectomized patients, which mainly presents with headache, motor weakness, and cognitive impairments. In these patients, cranioplasty improves these symptoms. Furthermore, patients without a classical SSFS have been shown to improve their neurological functions after reconstructive surgery. Amongst the many different pathophysiological theories proposed, the changes of CBP caused by the cranial defect might have a role in the neurological deficiencies. We have studied CBP in twelve cortical areas of both hemispheres, using 99mTc-HMPAO SPECT-CT before and after cranioplasty.METHODS: Twenty-eight craniectomized patients subject to reconstructive surgery were studied with 99mTc- HMPAO in three different times, before cranioplasty, a week after, and three months later. The images were processed with quantification software comparing CBP of 24 cortical areas with a reference area , and with a database of normal individuals. A mixed effects model was used to determine the signification of CBP changes in the cortex regions of both the damaged and undamaged brain hemispheres.RESULTS: CBP increased significantly in both hemispheres after cranioplasty both in ratio (β=0.019 p-value=0,030 first post-surgical SPECT-CT and β=0.021 p-value=0,015 in the second study, vs. pre-surgical) and Z-score (β=0.220 p-value=0,026 and β=0.279 p-value=0,005 respectively). Nine of twelve areas of the damaged side had a significant lower CBP ratio and Z-score than the undamaged. Posterior cingulate showed an increased CBP ratio (p-value=0,034) and Z-score(p-value0,028) in the first post-surgical SPECT-CT.CONCLUSION: CBP changes significantly in specific cortical areas after cranioplasty, which might explain the clinical improvements observed. Posterior cingulate changes might explain some improvements in attention impairments described. 99mTc-HMPAO SPECT-CT might be a valid tool to assess CBP changes in these patients and could have a role in the management of craniectomized individuals.CLINICAL TRIAL REGISTRATIONNot applicable

Atlas of 99mTc-HMPAO SPECT brain perfusion in pediatric brain disorders

Background: Blood flow to the brain is in parallel with brain metabolism in almost all brain disorders except in brain tumors and therefore regional cerebral blood flow can be used as a marker of metabolic brain activity and hence it is closely linked to neuronal activity, the activity distribution is presumed to reflect neuronal activity levels in different areas of the brain. Purpose: The aim of this work is to demonstrate to pediatrician in general and pediatric neurologist in particular the variations in cerebral perfusion during normal development which should be taken into consideration at the time of interpreting SPECT brain perfusion scan in different pediatric brain disorders. Method: Brain SPECT was performed 10 minutes after an intravenous injection of 11.1 MBq/kg (0.3 mCi/kg), and the minimum dose is 185 MBq (5 mCi) of 99mTc-HMPAO (4). Results: This was a retrospective analysis of SPECT brain perfusion scan of pediatric patients performed between October 2015 and December 2019 at our institution. We selected normal and abnormal studies in pediatric population with age range (5 months - 14 years). Conclusion: Although anatomic cross sectional imaging give details of neurological structural changes, SPECT perfusion mirrors indirectly both metabolic and neuronal activity changes. Therefore, accurate interpretation of SPECT perfusion will consolidate its role as part of the diagnostic protocol and used when the findings of other imaging modalities do not explain the symptoms or fail partially or completely in determining the etiology of brain disorders in pediatric patients.

Reduced regional cerebral blood flow measured by 99mTc-HMPAO SPECT in microgravity simulated by 5-day dry immersion

Purpose Neuro-ophthalmological changes defined as spaceflight-associated neuro-ocular syndrome have been reported after long duration space flights. The pathophysiology of this syndrome remains unclear, with the possible involvement of elevated intracranial pressure. Changes in blood flow in the brain, evaluated indirectly by Doppler, have been reported in flight. However, the effects of microgravity on regional cerebral blood flow (rCBF) are not known. We therefore investigated changes in rCBF in a 5-day dry immersion (DI) model. Moreover, we tested thigh cuffs as a countermeasure to prevent potential microgravity-induced modifications in rCBF.Methods 18 healthy male participants underwent 5-day DI with or without a thigh cuffs countermeasure. They were randomly allocated to a control (n = 9) or cuffs (n = 9) group. rCBF was measured 4 days before DI (Pre-DI) and at the end of the fifth day of DI (Post-DI), using single-photon emission computed tomography (SPECT) with radiopharmaceutical 99mTc-hexamethyl propylene amine oxime (HMPAO). SPECT images were processed using statistical parametric mapping (SPM12) software.Results At DI5, we observed a significant decrease in rCBF in 32 cortical and subcortical patterns, with greater hypoperfusion in the occipital region (occipital peak level: z = 4.51, puncorr < 0.001) and basal ganglia (putamen peak level: z = 4.71, puncorr < 0.001; caudate nuclei peak level: z = 3.80, puncorr < 0.001). No significant difference was found between the control and cuffs groups on variations in rCBF at DI5.Conclusion 5-day DI induces a relative decrease in rCBF in cortical and subcortical regions. Nevertheless, the consequences of this decrease for brain function and mechanisms need further investigation.

Non-Epileptiform EEG Patterns in Non-Convulsive Status Epilepticus: Can Quantified SPECT Imaging be Useful?

Background: The diagnosis of non-convulsive status epilepticus (NCSE) in patients with non-epileptiform EEG patterns remains a challenge. Objective: To prove the usefulness of single photon emission computerized tomography (SPECT) and its quantification (QtSPECT) in co-localizing the abnormal focus in the EEG with an area of hyperperfusion, thus helping in the diagnosis of NCSE.Methods: We retrospectively reviewed patients admitted with clinical suspicion of NCSE who underwent an HMPAO-SPECT controlled by scalp-EEG showing non-epileptiform patterns, in a 5-year period. We divided our patients in confirmed NCSE (n=11) and non-NCSE (n=8), and compared the EEG and SPECT results in both groups.Results: Lateralized rhythmic delta activity (LRDA) was predominant in the NCSE group (45’4%, p=0’045), while lateralized irregular slowing was observed equally in both groups. Patients with NCSE showed significant hyperperfusion compared to non-NCSE patients (p=0.026). QtSPECT correctly classified 91% of patients in NCSE and 75% patients with non-NCSE (p=0.006).Conclusions: Regional cerebral blood flow measured with SPECT could be useful in the diagnosis of NCSE in cases of an EEG pattern with lateralized slow activity and high clinical suspicion.