Technetium-99m Hexamethylpropylene Amine Oxime Research Articles

The [99mTc]Tc-HMPAO-labelled white blood cell SPECT/CT as a novel criterion for infective endocarditis diagnosis

Aims: Infective endocarditis (IE) poses a significant clinical challenge, necessitating nuanced diagnostic tools for early and accurate detection. The diagnostic role of the hybrid technique of single-photon emission tomography-computed tomography with technetium-99 m-hexamethylpropyleneamine oxime–labelled leukocytes ([99mTc]Tc-HMPAO-SPECT/CT) has evolved in recent years. This single-center study assessed whether the recent inclusion in the 2023 European Society of Cardiology modified diagnostic criteria of IE (2023 ESC) of infectious lesions detected with [99mTc]Tc-HMPAO-SPECT/CT affects their diagnostic performance.Methods and results: Between 2015 and 2019, we enrolled 205 consecutive adults with suspected IE. All participants underwent [99mTc]Tc-HMPAO-SPECT/CT scans (370–740 MBq). Scans were deemed positive in the presence of intracardiac abnormal tracer uptake and/or within the cardiac implantable electronic device. Patients were prospectively followed-up for 12 ± 10 months. Local device infection (LDI) or IE was diagnosed in 75 (36.6 %) patients, while 72 (35.1 %) [99mTc]Tc-HMPAO-SPECT/CT results returned positive. Moreover, extracardiac infectious foci were detected in 25 % of [99mTc]Tc-HMPAO-SPECT/CT scans. The inclusion of both intracardiac and extracardiac lesions detected with [99mTc]Tc-HMPAO-SPECT/CT yields significantly higher sensitivity (p = 0.003) and negative predictive value (NPV) (p = 0.009).Conclusion: The inclusion of [99mTc]Tc-HMPAO-SPECT/CT into the IE diagnostic work-up improves the appropriate classification of patients. For patients with IE, the extended inclusion of lesions detected with [99mTc]Tc-HMPAO-SPECT/CT in the ESC 2023 diagnostic criteria significantly improves sensitivity and NPV while reducing potential IE misdiagnoses. This pioneering imaging modality is poised to become an integral component of clinical practice, promising to advance IE diagnosis and management.

First-in-human infection imaging with 89Zr-labelled leukocytes and comparison of scan quality with [99mTc]Tc-HMPAO-labelled leukocytes

IntroductionNuclear medicine infection imaging is routinely performed with the use of leukocytes radiolabelled with technetium-99m hexamethylpropyleneamine oxime ([99mTc]Tc-HMPAO) and single-photon emission computed tomography (SPECT). Positron emission tomography (PET) is more sensitive than SPECT and results in higher-quality images. Zirconium-89 (89Zr) is a positron emitter with a half-life of 78.4 h, which translates to the biological half-life and slow biodistribution of intact cells and allows delayed PET imaging for more accurate biodistribution of the labelled leukocytes to infection foci. A first-in-human study with [89Zr]Zr-oxine-leukocytes in four healthy volunteers was reported in 2022. Our first-in-human study utilising the cell surface labelling approach aimed to image infection in patients with the use of 89Zr-labelled leukocytes, using p-isothiocyanatobenzyl-desferrioxamine B (Df-Bz-NCS) as a bifunctional chelating agent, and to compare the scan quality and biodistribution of [89Zr]Zr-Df-Bz-NCS-labelled leukocytes on PET images to SPECT images obtained with [99mTc]Tc-HMPAO-labelled leukocytes.MethodsLeukocytes were isolated from whole-blood samples of eight patients with clinically and/or radiologically confirmed infection. Isolated leukocytes were labelled with [99mTc]Tc-HMPAO according to standardised methods, and [89Zr]Zr-Df-Bz-NCS according to our previously published radiolabelling method. Whole-body SPECT imaging was performed 2 and 18 h post injection of [99mTc]Tc-HMPAO-labelled leukocytes, and whole-body PET/CT was performed 3 and 24 h post injection of [89Zr]Zr-Df-Bz-NCS-labelled leukocytes in seven patients.ResultsSuccessful [89Zr]Zr-Df-Bz-NCS-leukocyte labelling was achieved. High labelling efficiencies were obtained (81.7% ± 3.6%; n = 8). A mean high viability of [89Zr]Zr-Df-Bz-NCS-labelled leukocytes was observed (88.98% ± 12.51%). The [89Zr]Zr-Df-Bz-NCS-leukocyte labelling efficiency was not significantly affected by the white blood cell count of the patient. The performance of [99mTc]Tc-HMPAO- and [89Zr]Zr-Df-Bz-NCS-labelled leukocytes, in terms of the ability to accurately detect infection, were similar in two out of seven patients, and [99mTc]Tc-HMPAO-labelled leukocytes outperformed [89Zr]Zr-Df-Bz-NCS-labelled leukocytes in one patient with femoral osteomyelitis. However, in two cases of pulmonary pathology, [89Zr]Zr-Df-Bz-NCS-labelled leukocytes demonstrated improved pathological uptake. No skeletal activity was observed in any of the patients imaged with [89Zr]Zr-Df-Bz-NCS-labelled leukocytes, illustrating the in vivo stability of the radiolabel.DiscussionAlthough the [89Zr]Zr-Df-Bz-NCS-leukocyte labelling aspect of this study was noteworthy, infection imaging did not yield convincingly positive results due to the pulmonary trapping of intravenously administered [89Zr]Zr-Df-Bz-NCS-labelled leukocytes.

Impact of Fat Distribution and Metabolic Diseases on Cerebral Microcirculation: A Multimodal Study on Type 2 Diabetic and Obese Patients.

Background: Since metabolic diseases and atherosclerotic vascular events are firmly associated, herein we investigate changes in central microcirculation and atherosclerosis-related body fat distribution in patients with type 2 diabetes mellitus and obesity. Methods: Resting brain perfusion single-photon emission computed tomography (SPECT) imaging with Technetium-99m hexamethylpropylene amine oxime ([99mTc]Tc-HMPAO SPECT) was performed, and the breath-holding index (BHI) and carotid intima-media thickness (cIMT) were measured to characterise central microcirculation. Besides CT-based abdominal fat tissue segmentation, C-peptide level, glycaemic and anthropometric parameters were registered to search for correlations with cerebral blood flow and vasoreactivity. Results: Although no significant difference was found between the resting cerebral perfusion of the two patient cohorts, a greater blood flow increase was experienced in the obese after the breath-holding test than in the diabetics (p < 0.05). A significant positive correlation was encountered between resting and provocation-triggered brain perfusion and C-peptide levels (p < 0.005). BMI and cIMT were negatively correlated (rho = -0.27 and -0.23 for maximum and mean cIMT, respectively), while BMI and BHI showed a positive association (rho = 0.31 and rho = 0.29 for maximum and mean BHI, respectively), which could be explained by BMI-dependent changes in fat tissue distribution. cIMT demonstrated a disproportional relationship with increasing age, and higher cIMT values were observed for the men. Conclusions: Overall, C-peptide levels and circulatory parameters seem to be strong applicants to predict brain microvascular alterations and related cognitive decline in such patient populations.

Advances in Molecular Imaging in Infective Endocarditis.

Infective endocarditis (IE) is a growing epidemiological challenge. Appropriate diagnosis remains difficult due to heterogenous etiopathogenesis and clinical presentation. The disease may be followed by increased mortality and numerous diverse complications. Developing molecular imaging modalities may provide additional insights into ongoing infection and support an accurate diagnosis. We present the current evidence for the diagnostic performance and indications for utilization in current guidelines of the hybrid modalities: single photon emission tomography with technetium99m-hexamethylpropyleneamine oxime-labeled autologous leukocytes (99mTc-HMPAO-SPECT/CT) along with positron emission tomography with fluorodeoxyglucose (18F-FDG PET/CT). The role of molecular imaging in IE diagnostic work-up has been constantly growing due to technical improvements and the increasing evidence supporting its added diagnostic and prognostic value. The various underlying molecular processes of 99mTc-HMPAO-SPECT/CT as well as 18F-FDG PET/CT translate to different imaging properties, which should be considered in clinical practice. Both techniques provide additional diagnostic value in the assessment of patients at risk of IE. Nuclear imaging should be considered in the IE diagnostic algorithm, not only for the insights gained into ongoing infection at a molecular level, but also for the determination of the optimal clinical therapeutic strategies.

13-cis-Retinoic Acid Affects Brain Perfusion and Function: In Vivo Study

Purpose. Study the effects of 13-cis-retinoic acid (13-RA), a synthetic analogue of a vitamin A used for the treatment of severe acne, on the blood flow in the rat brain using technetium-99m hexamethyl propylene amine oxime (99mTc-HMPAO) imaging. Methods. A total of 30 adult male Wistar rats were divided into the control (C), low-dose (L), and high-dose (H) groups. The L and H rats were exposed subcutaneously to 0.3 and 0.5 mg, respectively, of 13-RA per kg of body weight for seven days. Brain blood flow imaging was performed using a gamma camera. Then, a region of interest (ROI) around the brain (target, T), a whole-body region (WB), and a background region (BG) was selected and delimited. The net 99mTc-HMPAO brain counts were calculated as the net target counts, [Formula: see text] in all groups. At the end of the 99mTc-HMPAO brain blood flow imaging, the brain, heart, kidney, lung, and liver were rapidly removed, and their uptake was determined. Brain histopathological analysis was performed using hematoxylin and eosin stains. In addition, the plasma fatty acids were studied using gas chromatography/mass spectrometry. Results. There were highly significant differences between L and H in comparison to C and across the groups. The 99mTc-HMPAO radioactivity in the brain showed increased uptake in a dose-dependent manner. There were also significant changes in the brain tissues and decreased free fatty acids among the groups compared to C. Conclusion. 13-RA increases 99mTcHMPAO brain perfusion, uptake, and function and reduces fatty acids.

To what extent does prior antimicrobial therapy affect the diagnostic performance of radiolabeled leukocyte scintigraphy in infective endocarditis?

AimsThis prospective, single-center study sought to assess to what extent there is interference between the hybrid technique of single-photon emission tomography-computed tomography with technetium99m-hexamethylpropyleneamine oxime–labeled leukocytes (99mTc-HMPAO-SPECT/CT) and antimicrobial therapy in patients with infective endocarditis (IE). Methods and resultsDuring the years 2015–2019, we enrolled 205 consecutive adults with suspected IE, all underwent 99mTc-HMPAO-SPECT/CT. The study population was divided into those who had received antimicrobial therapy up to 30 days prior to 99mTc-HMPAO-SPECT/CT (group 1, n = 96) and those who had not (group 2, n = 109). Patients were prospectively observed for 12 ± 10 months. Group 1 presented higher positive predictive values (91.89% vs. 60.00%, = 0.001), and decreased negative predictive values (77.97% vs. 90.54%, P = 0.04). Patients treated with antimicrobial therapy displayed false-negative 99mTc-HMPAO-SPECT/CT results more often [odds ratio (OR), 4.63; 95% confidence interval (CI), 1.41–15.23, P = .01], particularly when intravenous (OR 5.37; 95% CI 1.73–16.62, P = .004), definite (OR 9.43; 95% CI 2.65–33.51, P = .001), and combination antibiotic regimens (OR 8.1; 95% CI 2.57–25.64, P = .001) had been administered. ConclusionPrior antibiotic therapy affects 99mTc-HMPAO-SPECT/CT diagnostic properties. Patients treated with antimicrobial therapy display false-negative 99mTc-HMPAO-SPECT/CT results more often, especially if intravenous, definite, or combination regimens are administered. Graphical abstract▪

Regional Cerebral Blood Flow Correlates of Neuropsychiatric Symptom Domains in Early Alzheimer's Disease.

Although various neuropsychiatric symptoms are frequently accompanied with Alzheimer’s disease (AD) and pose a substantial burden to both patients and caregivers, their neurobiological underpinnings remain unclear. This study investigated associations between regional cerebral blood flow (rCBF) and neuropsychiatric symptom domains in early AD. A total of 59 patients with early AD underwent brain technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) single-photon emission computed tomography (SPECT) scans. Neuropsychiatric symptoms were assessed by the Neuropsychiatric Inventory and clustered into the affective, apathy, hyperactivity, and psychotic domains. A voxel-wise multiple regression analysis was performed with four domain scores as independent variables and age, sex, and Mini-Mental State Examination scores as covariates. The affective domain score was negatively correlated with rCBF in the prefrontal cortex, thalamus, and caudate. The apathy domain score showed inverse correlations with rCBF in the prefrontal and pre/postcentral gyri and midbrain. Patients with higher hyperactivity domain scores had increased rCBF in the prefrontal and temporal lobes. The psychotic symptom domain was positively correlated with rCBF in the cuneus and negatively associated with rCBF in the prefrontal, cingulate, and occipital regions and putamen. The score of each neuropsychiatric symptom domain showed the differential correlates of brain perfusion, while altered rCBF in the prefrontal cortex was found in all domains. Although preliminary, our results may suggest common and distinct patterns of rCBF underlying neuropsychiatric symptoms in early AD. Further studies with larger samples and control participants are warranted to confirm these findings.

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.

Improvements of Frontotemporal Cerebral Blood Flow and Cognitive Functioning in Patients With First Episode of Schizophrenia Treated With Long-Acting Aripiprazole.

Frontal and temporal cerebral blood flow (CBF) changes are the most common impairments of CBF described in patients with schizophrenia. Those impairments have also been associated with cognitive deficits, a hallmark of schizophrenia. In light of that fact, treatment interventions should target cognitive deficits to prevent chronic disability. However, specific therapies targeting cognitive symptoms are very few and far between. One of the treatment possibilities is aripiprazole, because several studies reported its potential procognitive effects. The objective of this study was to investigate whether use of aripiprazole in its long-acting injectable formulation (ALAI), during a 3-month treatment, has beneficial effects on CBF and cognitive functioning in patients with first episode of schizophrenia. Single-photon emission computed tomography with technetium-99m hexamethylpropylene amine oxime was performed at 2 time points. Cognitive functions were assessed with a standardized test for cognitive functions, 5-KOG test, whereas severity of clinical symptoms was assessed with the Positive and Negative Syndrome Scale, both at the same 2 time points as single-photon emission computed tomography. Three-month treatment with ALAI was associated with improvement of several cognition indices and improvements of right-sided frontal and temporal CBF, as well as of clinical symptoms. Multivariate tests were used to test for the effects of ALAI treatment on cognitive functions, clinical presentation, and brain perfusion in a 3-month period. Multivariate model revealed statistical significance (F = 11.958, P < 0.001). Of 10 separate 5-KOG parameters, 3-month treatment with ALAI significantly influenced 4: undelayed recall, delayed recall, attention, and working memory-digit span forward. Finally, 3-month ALAI treatment significantly improved regional CBF in 2 of 4 investigated areas, both on the right side of the brain (frontally and temporally). Results of this research showed that treatment with ALAI in patients with first episode of schizophrenia is associated with improved right-sided frontal and temporal CBF, as well as with improved symptoms, including cognition indices. Although we cannot confirm it directly, it is possible that improved frontotemporal CBF led to the improvement in cognition indices.

Possible neuroprotective effects of rasagiline in Alzheimer's disease: a SPECT study.

The current lack of effective treatments for Alzheimer's disease (AD) and the rapidly increasing burden of the disease highlight the urgent need to find new treatments. Despite accumulating evidence of the beneficial effects of rasagiline in neurodegenerative diseases such as Parkinson's disease, the effects of rasagiline on the brains of patients with AD have not been elucidated. To examine the effects of rasagiline on regional cerebral flow (rCBF) in patients with AD using single photon emission computed tomography (SPECT). Among 22 patients with AD, 11 patients received adjunctive rasagiline at 1 mg/day in conjunction with acetylcholinesterase inhibitors (AChEI); 11 patients were only treated with AChEI for about 1.6 years. All patients underwent brain technetium-99m hexamethylpropylene amine oxime SPECT scans and clinical assessments at baseline and follow-up visits. Annual percent changes in rCBF were compared between the groups in a voxel-wise manner. SPECT analysis revealed that the rasagiline-treated group showed more increased rCBF in the cingulate gyrus, inferior frontal gyrus, putamen, and thalamus compared to the comparison group (P < 0.005). We demonstrated that adjunctive rasagiline treatment may have beneficial effects on brain perfusion in patients with AD, suggesting potential neuroprotective effects.

The Prognostic Value of 99mTc-HMPAO-Labeled Leucocyte SPECT/CT in Cardiac Device-Related Infective Endocarditis

ObjectivesThis was a prospective, single-center study designed to assess the prognostic value of the hybrid technique of single photon emission tomography and computed tomography with the application of technetium99m-hexamethylpropyleneamine oxime–labelled autologous leukocytes (99mTc-HMPAO-SPECT/CT) in patients with cardiac device-related infective endocarditis (CDRIE). BackgroundCDRIE entails the risk of complications and an increase in mortality rates, both in-hospital and long-term. The prognostic value of 99mTc-HMPAO-SPECT/CT in the course of CDRIE has not been evaluated so far. MethodsThe project enrolled 103 consecutive patients with suspected CDRIE, all of whom underwent 99mTc-HMPAO-SPECT/CT. The resulting scans were then classified as positive if the presence of abnormal tracer uptake involving cardiac and intravascular sections of the device electrodes was found. Patients were prospectively observed for a mean time of 17.48 ± 11.9 months. All-cause mortality, in-hospital mortality, and complete hardware removal were assessed, followed by a composite endpoint including complications, namely embolic events, new onset heart failure, uncontrolled infection, renal replacement therapy, reoperation, new heart rhythm, and conduction disturbances. ResultsIn the analysis, despite a noticeable trend, all-cause mortality rates were not found to be statistically significantly higher among the 35 patients who registered positive results using 99mTc-HMPAO-SPECT/CT for CDRIE (group 1) than among the 68 patients from group 2 whose 99mTc-HMPAO-SPECT/CT results were negative (20% vs. 10.3%, respectively; p = 0.14). However, group 1 did present higher in-hospital mortality (11.4% vs. 0%, respectively; odds ratio: 19.6; 95% confidence interval [CI]: 1.02 to 374.70), an increased rate of complications (43% vs. 9%, respectively; hazard ratio [HR]: 5.9; 95% CI: 2.27 to 15.20), and underwent hardware removal more frequently (57% vs. 16%, respectively; HR: 4.3; 95% CI: 2.07 to 19.08). ConclusionsIn patients with suspected CDRIE, positive 99mTc-HMPAO-SPECT/CT results were associated with increased rates of in-hospital mortality and complications.

MRI and Technetium-99m Hexamethylpropylene Amine Oxime Labeled Leucocyte Scintigraphy in the Diagnosis and Differentiation between Acute Osteomyelitis and Neuroarthropathy in the Diabetic Foot

Abstract Background: Soft tissue and bone infection and neuro osteoarthropathy involving the foot are the most common long-term complications of diabetes mellitus, implying a serious impairment in quality of life for patients in the advanced stages of the disease. Both pathologies often coexist and differentiating between them is crucial because the management may differ substantially. Misdiagnosis may result in high morbidity for the patient such as unnecessary limb amputation. Diagnosis is largely based on clinical signs supplemented by various imaging modalities such as radiography, MR imaging, and hybrid imaging techniques such as F-18 fluorodeoxyglu-cose-positron emission tomography and nuclear imaging studies. Aim of Study: The aim of this study is to evaluate the diagnostic value of MRI and technetium-99m Hexamethyl-propylene Amine Oxime (HMPAO) labeled leukocyte scin-tigraphy in the diagnosis and differentiation between acute osteomyelitis and neuroarthropathy in the diabetic foot. Patients and Methods: The study included 35 patients (20 men and 15 women) aged 62±8.8 years having diabetes mellitus and a total of 43 clinically suspicious infection sites. The basic exploration included standard radiography, three-phase bone scintigraphy and 99mTc-HMPAO Leucocyte Scan (HMPAO-LS) and pre and post contrast enhanced MRI. 16 bone and 10 soft tissue biopsies were obtained from ulceration sites. Clinical follow-up as well as scintigraphy and MRI performed 4 months after initial diagnosis and 1 month after antibiotic withdrawal were performed in suspected osteomy-elitis cases. Results: Among the 43 sites, 23 sites were finally diag-nosed as osteomyelitis. No osteomyelitis was present at 20 sites, of which 9 sites were diagnosed as cellulitis and 11 as neuropathic ulcers based on combined clinical, imaging, pathologic findings and follow-up. The sensitivity and specif-icity of MRI were (95% and 85%) and of Labeled leucocyte scanning were (87% and 90%) respectively.Conclusion: The combined use of 99mTc-HMPAO-LS and MRI yielded higher diagnostic efficacy in diabetic foot related complications.

P1294 Distribution of infective lesions detected with radiolabeled leucocyte scintigraphy in carriers of various types of cardiac implantable electronic devices

Abstract Funding Acknowledgements Grant from the Jagiellonian University Medical College (K/DSC/004383) Background The rate of cardiac device-related infective endocarditis (CDRIE) is increasing disproportionately to the rising rate of device implantations. Hybrid technique of single photon emission tomography and computed tomography with technetium99m-hexamethylpropyleneamine oxime–labeled autologous leukocytes (99mTc-HMPAO-SPECT/CT) is a developing technique in patients with suspected endocarditis. Purpose The aim of this study was to evaluate distribution of both intracardiac and extracardiac inflammatory lesions detected with 99mTc-HMPAO-SPECT/CT in patients with suspected CDRIE depending on the type of carried cardiac implantable electronic device (CIED). Methods During years 2015-2018, we prospectively enrolled 103 consecutive patients with suspected CDRIE (70 males, 61 ± 18 y.o.). Patients undergone evaluation according to current ESC guidelines and subsequently 99mTc-HMPAO-SPECT/CT. Scans were classified as positive in the presence of abnormal tracer uptake involving cardiac or/and intravascular sections of device electrodes. Patients were divided to group 1 with implanted pacemakers (61 patients) and group 2 including 42 carriers of either an implantable cardioverter-defibrillator (ICD) or a cardiac resynchronization therapy device (CRT). Results Overall, in group 2 there was a higher prevalence of diabetes mellitus, coronary artery disease and heart failure (p &amp;lt; 0.05). Moreover, group 2 had worse functional status with higher NYHA class (2.8 ± 0.9 vs. 1.7 ± 1, p = 0.001), NT-proBNP levels (5027 ± 5813 vs. 2320 ± 4279, p = 0.0004) and lower left ventricle ejection fraction (29 ± 12 vs. 54 ± 13, p = 0.0001). Both groups had comparable values of C-reactive protein, procalcitonin and white blood cells (p &amp;gt; 0.05). The mean time since device implantation was 3.4 ± 3.8 years and on average patients had 1.9 implanted electrodes. Patients from group 2 presented more often with 99mTc-HMPAO-SPECT/CT positive for CDRIE (45% vs. 26%, p = 0.045). Frequency of lesions consistent with infection localized within the intravascular section of the electrode and the CIED lodge did not differ between groups (p &amp;gt; 0.05). However, inflammatory foci in the vicinity of the intracardiac portion of the electrode were detected more often in group 2 (43% vs. 21%, p = 0.019). Overall, extracardiac inflammatory foci were found in 34% of patients, with most common localization in the gastrointestinal tract (13%) and musculoskeletal system (8%). Both prevalence and localization of extracardiac foci did not differ between groups (39% vs. 24%, p = 0.16). Conclusions Prevalence and localization of intracardiac inflammatory foci typical for CDRIE detected with 99mTc-HMPAO-SPECT/CT is different in patients with various types of CIEDs. Patients with implanted ICD or CRT have worse functional status and present more frequently with radiotracer uptake typical for CDRIE in 99mTc-HMPAO-SPECT/CT. Distribution of extracardiac inflammatory lesions does not differ between groups.

The role of 99mTc-HMPAO-labelled white blood cell scintigraphy in the diagnosis of cardiac device-related infective endocarditis.

The hybrid technique of single-photon emission tomography and computed tomography with technetium99m-hexamethylpropyleneamine oxime-labelled leucocytes (99mTc-HMPAO-SPECT/CT) is an emerging diagnostic technique in patients with cardiac device-related infective endocarditis (CDRIE). This prospective study assessed the 99mTc-HMPAO-SPECT/CT diagnostic profile and its added value to the modified Duke criteria (mDuke) in CDRIE diagnostic work-up. The study examined 103 consecutive patients with suspected CDRIE, who underwent 99mTc-HMPAO-SPECT/CT. Diagnostic accuracy was calculated based on a final clinical CDRIE diagnosis, including microbiology, echocardiography, and a 6-month follow-up. Subsequently, we compared the diagnostic value of the initial mDuke classification with a classification including 99mTc-HMPAO-SPECT/CT positive results as an additional major CDRIE criterion: mDuke-SPECT/CT.Overall, CDRIE was diagnosed in 31 (31%) patients, whereas 35 (34%) 99mTc-HMPAO-SPECT/CT were positive. 99mTc-HMPAO-SPECT/CT was characterized by 86% accuracy, 0.69 Cohen's kappa coefficient, 84% sensitivity, 88% specificity, 93% negative, and 74% positive predictive values. The original mDuke displayed 83% accuracy, 0.52 kappa, whereas mDuke-SPECT/CT had 88% accuracy, and 0.73 kappa. Compared with mDuke, mDuke-SPECT/CT showed significantly higher sensitivity (87% vs. 48%, P < 0.001). According to mDuke, 49.5% of patients had possible CDRIE, and after reclassification, that figure dropped to 37%. Furthermore, having assessed the diagnosis categorization improvement following the incorporation of 99mTc-HMPAO-SPECT/CT, the net reclassification index value was found to be 31.4%. In patients with CDRIE, 99mTc-HMPAO-SPECT/CT provides high diagnostic accuracy, whereas a negative scan excludes CDRIE with high probability. Inclusion of 99mTc-HMPAO-SPECT/CT into mDuke diagnostic criteria yields significantly higher sensitivity and a reduction in possible CDRIE diagnoses.

Imaging tests for the detection of osteomyelitis: a systematic review.

Osteomyelitis is an infection of the bone. Medical imaging tests, such as radiography, ultrasound, magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT) and positron emission tomography (PET), are often used to diagnose osteomyelitis. To systematically review the evidence on the diagnostic accuracy, inter-rater reliability and implementation of imaging tests to diagnose osteomyelitis. We conducted a systematic review of imaging tests to diagnose osteomyelitis. We searched MEDLINE and other databases from inception to July 2018. Risk of bias was assessed with QUADAS-2 [quality assessment of diagnostic accuracy studies (version 2)]. Diagnostic accuracy was assessed using bivariate regression models. Imaging tests were compared. Subgroup analyses were performed based on the location and nature of the suspected osteomyelitis. Studies of children, inter-rater reliability and implementation outcomes were synthesised narratively. Eighty-one studies were included (diagnostic accuracy: 77 studies; inter-rater reliability: 11 studies; implementation: one study; some studies were included in two reviews). One-quarter of diagnostic accuracy studies were rated as being at a high risk of bias. In adults, MRI had high diagnostic accuracy [95.6% sensitivity, 95% confidence interval (CI) 92.4% to 97.5%; 80.7% specificity, 95% CI 70.8% to 87.8%]. PET also had high accuracy (85.1% sensitivity, 95% CI 71.5% to 92.9%; 92.8% specificity, 95% CI 83.0% to 97.1%), as did SPECT (95.1% sensitivity, 95% CI 87.8% to 98.1%; 82.0% specificity, 95% CI 61.5% to 92.8%). There was similar diagnostic performance with MRI, PET and SPECT. Scintigraphy (83.6% sensitivity, 95% CI 71.8% to 91.1%; 70.6% specificity, 57.7% to 80.8%), computed tomography (69.7% sensitivity, 95% CI 40.1% to 88.7%; 90.2% specificity, 95% CI 57.6% to 98.4%) and radiography (70.4% sensitivity, 95% CI 61.6% to 77.8%; 81.5% specificity, 95% CI 69.6% to 89.5%) all had generally inferior diagnostic accuracy. Technetium-99m hexamethylpropyleneamine oxime white blood cell scintigraphy (87.3% sensitivity, 95% CI 75.1% to 94.0%; 94.7% specificity, 95% CI 84.9% to 98.3%) had higher diagnostic accuracy, similar to that of PET or MRI. There was no evidence that diagnostic accuracy varied by scan location or cause of osteomyelitis, although data on many scan locations were limited. Diagnostic accuracy in diabetic foot patients was similar to the overall results. Only three studies in children were identified; results were too limited to draw any conclusions. Eleven studies evaluated inter-rater reliability. MRI had acceptable inter-rater reliability. We found only one study on test implementation and no evidence on patient preferences or cost-effectiveness of imaging tests for osteomyelitis. Most studies included < 50 participants and were poorly reported. There was limited evidence for children, ultrasonography and on clinical factors other than diagnostic accuracy. Osteomyelitis is reliably diagnosed by MRI, PET and SPECT. No clear reason to prefer one test over the other in terms of diagnostic accuracy was identified. The wider availability of MRI machines, and the fact that MRI does not expose patients to harmful ionising radiation, may mean that MRI is preferable in most cases. Diagnostic accuracy does not appear to vary with the potential cause of osteomyelitis or with the body part scanned. Considerable uncertainty remains over the diagnostic accuracy of imaging tests in children. Studies of diagnostic accuracy in children, particularly using MRI and ultrasound, are needed. This study is registered as PROSPERO CRD42017068511. This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 61. See the NIHR Journals Library website for further project information.

Noninvasive quantitation of rat cerebral blood flow using 99mTc-HMPAO\u2014assessment of input function with dynamic chest planar imaging

BackgroundCerebral blood flow (CBF) quantitation using technetium-99m hexamethylpropyleneamine oxime (99mTc-HMPAO) generally requires assessment of input function by arterial blood sampling, which would be invasive for small animals. We therefore performed chest dynamic planar imaging, instead of arterial blood sampling, to estimate the input function and establish noninvasive quantitation method of rat CBF using the image-derived input function.ResultsIntegrated radioactivity concentration in the heart-blood pool on planar images (AUCBlood-planar) was identical to that in arterial blood samples (AUCBlood-sampling). Radioactivity concentration in the brain determined by SPECT imaging (CBrain-SPECT) was identical to that using brain sampling (CBrain-sampling). Noninvasively calculated CBF obtained by dividing CBrain-SPECT by AUCBlood-planar was well correlated with conventionally estimated CBF obtained by dividing CBrain-sampling by AUCBlood-sampling.ConclusionRat CBF could be noninvasively quantitated using 99mTc-HMPAO chest dynamic planar imaging and head SPECT imaging without arterial blood sampling.

MRI Brain Findings in Adults with Lesional Refractory Epilepsy and Correlation to Surgical Outcome

Introduction: Refractory epilepsy which is defined as failure of adequate trials of two tolerated, appropriately chosen and used antiepileptic drug schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom is common in patients with structural brain lesions including acquired disorders and genetic abnormalities. High resolution Magnetic Resonance Imaging MRI of the brain has proven its precision as a diagnostic tool for recognition of different structural lesions underlying medically intractable seizures. Objective: To recognize common MRI lesions in a series of adult patients with refractory epilepsy admitted to the epilepsy monitoring unit at Prince Sultan Military Medical City PSMMC for pre surgical evaluation for epilepsy surgery with correlation to surgical outcome and to compare our local data with the international literature. Material and methods: 245 patients (100 Males and 145 Females; 14-53 years) with refractory epilepsy were included in this retrospective analysis. They presented with partial with or without complex partial seizures 112 (46.0%), partial with secondary generalized tonic clonic seizures 76 (31.0%) or generalized seizures in 57 (23.0%) of patients. Clinical diagnosis of epilepsy and seizure classification were based on the revised criteria of the International League Against Epilepsy ILAE. Structural neuroimaging MRI brain, functional neuroimaging which include Interictal Fluorodeoxyglucose Positron Emission Computed Tomography FDG-PET, Ictal Technetium-99m hexamethyl-propylene amine oxime Single Photon Emission Computed Tomography 99 m HMPAO SPECT, Electroencephalography EEG recording, epilepsy history and neurological examination were performed. MRI brain imaging epilepsy protocol used a 1.5 or 3 Tesla MRI scanner. All patients included in this study received appropriate epilepsy surgery and post-operative seizure control was followed in the epilepsy clinic with six-month post-operative inter ictal EEG, follow up MRI brain after epilepsy surgery were performed in all patients and 50 patients had additional video-EEG recording postoperative during the follow up period. Epilepsy surgery seizure control outcome was classified according to Engel Classification system. All patients were followed for at least two years post-operatively to assess seizure control. Pre-operative MRI diagnosis was correlated with the epilepsy surgery seizure control outcome. Results: MRI detected different structural brain abnormalities in 245 (100%) patients, including temporal lobe location in 142 (58%) patients, frontal lobe location in 74 (30%) patients and parieto-occipital lobes location in 29 (12%) patients. On MRI hippocampal sclerosis HS is diagnosed in 86 (35%) patients, cerebral tumors in 74 (30%) patients and among the cerebral tumors MRI suggested the diagnosis of developmental tumors that is; glio-neural tumors in 45 out of 74 (61%) of tumor patients, malformations of cortical development MCD in 42 (17%) patients, vascular malformations in 15 (6%) patients, dual pathologies in 12 (5%) patients and remote gliotic lesions in 16 (7%) patients. The histopathological diagnosis confirmed the MRI brain diagnosis in all included patients. At 2 years of post-operative follow-up 196 (80%) patients were classified as Engel Class I, 37 (15%) patients Engel Class II, 6 (3%) patients Engel Class III and 6 (3%) patients as Class IV seizure freedom. In the class IV group two patients failed epilepsy surgery because they had high grade astrocytoma with postoperative tumor recurrence and four patients failed epilepsy surgery due to incomplete resection of epileptogenic lesions. Patients with MRI diagnosis of HS 82 out of 86 (95%) patients, low grade tumor 59 out of 74 (80%) patients and vascular malformation 12 out of 15 (80%) had best epilepsy surgery outcome. Patients with high grade tumors 2 out 3 (67%) patients and incomplete surgical resection of epileptogenic lesions 4 out of 5 (80%) patients had the worst epilepsy surgery outcome. Conclusion: This study revealed that MRI brain structural lesions were commonly associated with refractory epilepsy. Temporal lobe structural brain lesions were most common lesions in adult epilepsy patients with refractory epilepsy referred for epilepsy surgery. The presence of HS, low grade tumors and vascular malformations correlated with best surgical outcome while high grade tumors and incomplete surgical resection of the lesions correlated with worst surgical outcome. Our results were consistent with the international reported literature.

Brain Perfusion Correlates of Apathy in Alzheimer's Disease.

Background and PurposeApathy is one of the most common neuropsychiatric symptoms in patients with Alzheimer's disease (AD). It may have adverse impacts on the progression of AD. However, its neurobiological underpinnings remain unclear. The objective of this study was to investigate differences in regional cerebral blood flow (rCBF) between AD patients with apathy and those without apathy.MethodsSixty-six apathetic AD patients and 66 AD patients without apathy completed Neuropsychiatric Inventory (NPI) and underwent technetium-99m hexamethylpropylene amine oxime single-photon emission computed tomography (SPECT) scans. Voxel-wise differences in rCBF between the 2 groups were examined. Association between rCBF and levels of apathy in the apathetic group was also assessed.ResultsAD patients with apathy showed lower rCBF in the bilateral orbitofrontal cortex, left putamen, left nucleus accumbens, left thalamus, and bilateral insula than those without (all p<0.005). Mean perfusion across all significant clusters showed a negative linear correlation with NPI apathy score in AD patients with apathy (β=−0.25; p=0.04).ConclusionsHypoperfusion in the prefrontal, striatal, and insular areas may be neural correlates of apathy in AD patients.

Fibroblast Growth Factor Type 1 (FGF1)-Overexpressed Adipose-Derived Mesenchaymal Stem Cells (AD-MSCFGF1) Induce Neuroprotection and Functional Recovery in a Rat Stroke Model.

Stroke, as the second most common cause of death, imposes a great financial burden on both the individual and society. Mesenchymal stem cells from rodents have demonstrated efficacy in experimental animal models of stroke due to enhanced neurological recovery. Since FGF1 (fibroblast growth factor 1) displays neuroprotective properties, for the first time, we investigated the effect of acute intravenous administration of FGF1 gene transfected adipose-derived mesenchymal stem cell (AD-MSCFGF1) on transient experimental ischemic stroke in rats. Stroke induction was made by transient middle cerebral artery occlusion (tMCAO). 2 × 106AD-MSCFGF1 was administrated intravenously 30min after carotid reperfusion. The ability of technetium99m-hexamethyl propylene amine oxime (99mTc-HMPAO)-labeled AD-MSCFGF1 to enter into ischemic brain was evaluated 2h post injection. 24h post operation, the neurological recovery (rotarod and Roger's tests), the infarct volume (2, 3, 5-triphenyltetrazolium chloride, TTC assay), apoptosis rate (TUNEL assay), and the expression of FGF1 protein (western blotting) in the ischemic hemisphere were assessed. The 99mTc-HMPAO-labeled AD-MSCFGF1 could enter into the ischemic brain. Ischemic hemisphere activity was significantly higher than that observed in the contralateral hemisphere (p = 0.002). The administration of AD-MSCFGF1 resulted in significant improvement of neurological function tests and increased density of FGF1 protein in the peri-infarct area, while the infarct volume and the apoptotic index were significantly decreased, in comparison to the other treated groups. In conclusion, acute intravenous administration of AD-MSCFGF1 can be a novel and promising candidate approach for the treatment of ischemic stroke.

The Implication of the Thalamus in Speech Disturbance in a Boy with Rolandic Epilepsy

Transient oromotor deficits in children with rolandic epilepsy (RE) have been described in literature. It has been reported that thalamic aphasia can be caused by thalamic infarction or hemorrhage; however, it has never been reported that thalamic aphasia can be caused by epileptic disorders. Here, we describe a 6-year-old right-handed boy who showed transient oromotor deficits and speech disturbance with worsening of both epileptic seizure and paroxysmal discharges on electroencephalogram. He had paucity of spontaneous speech, feeble speech, arrest of speech, and anomia, but his repetition skills were intact. A single-photon emission computed tomography (SPECT) scan using technetium-99m hexamethyl propylene amine oxime (99mTc-HMPAO) to measure regional cerebral blood flow showed a reduction in flow in the left thalamus and ipsilateral frontotemporal areas, which appeared concurrently with the speech dysfunction. We suggest that speech disturbance such as thalamic aphasia, which is similar to the symptoms of Landau-Kleffner syndrome, may occur due to epileptic disorders such as RE. It may be possible to miss speech disturbance implicated in the thalamus in cases complicated by oromotor dysfunction. It is important that speech disturbance implicated in the thalamus is not overlooked in patients with RE showing an atypical course.