99mTc-hexamethylpropyleneamine Oxime Research Articles

Surgical Outcomes of Low-Flow Bypass Surgery in Intracranial Atherosclerotic Steno-Occlusive Diseases.

The role of bypass surgery in intracranial atherosclerotic steno-occlusive diseases (ICADs) remains controversial. We aimed to analyze the surgical outcomes of bypass surgery in patients with the ICADs in a single tertiary institution. Among 1018 cases of low-flow bypass surgery between 2003 and 2022, 215 patients with the ICAD refractory to medical treatment were finally enrolled in this study. Clinical and radiological outcomes were retrospectively evaluated, with survival analyses. All strokes, cerebral infarctions, and intracranial hemorrhages occurred in 12.1% (n = 26), 9.8% (n = 21), and 2.3% (n = 5), respectively, during the clinical follow-up of 54.6 ± 47.6 months (range, 0.6-237.8 months). Among all stroke events, 84.6% (n = 22) occurred within 30 postoperative days. The 2-year and 5-year cumulative risks of all strokes were 12.1% each. The mean modified Rankin Scale scores were 1.6 ± 1.1 (range, 0-5) preoperatively and 0.8 ± 1.2 (range, 0-6) at last (P < .01). The patency of direct bypass was 99.1% (n = 213) just before discharge and 96.3% (n = 184 of 191 patients with available tests) at the last angiographic follow-up of 27.0 ± 27.3 months (range, 2.3-97.3 months). All the patients with available data (n = 190) showed hemodynamic improvement on acetazolamide-challenged single-photon emission computed tomography with 99mTc-hexamethylpropyleneamine oxime during the follow-up of 38.6 ± 36.7 months (range, 2.3-158.6 months). Low-flow bypass surgery showed acceptable treatment outcomes in the prevention of recurrent stroke.

РАЗРАБОТКА ПРОГРАММНЫХ СРЕДСТВ МАТЕМАТИЧЕСКОГО ИМИТАЦИОННОГО МОДЕЛИРОВАНИЯ НА ОСНОВЕ КЛИНИЧЕСКИХ ДАННЫХ И ФАНТОМНЫХ ИССЛЕДОВАНИЙ ДЛЯ ОЦЕНКИ ПЕРФУЗИИ ГОЛОВНОГО МОЗГА И ПОВЫШЕНИЯ КАЧЕСТВА ИЗОБРАЖЕНИЙ ПРИ ОФЭКТ/КТ С 99MTC-ГМПАО

Purpose: To develop a software package Virtual examination of brain perfusion by the method of SPECT/CT with 99mTc-HMPAO (Teoxime) and its practical application to study the conditions for achieving the best image quality in clinical studies of patients. Material and methods: The studies were performed using clinical data and the method of computer simulation. Clinical data of single-photon emission computed tomography combined with X-ray computed tomography (SPECT/CT) with 99mTc-hexamethylpropyleneamine oxime (99mTc-Teoxime, produced by DIAMED LLC) of a patient with an ischemic stroke of the right frontal cortex were obtained on a two-detector gamma-camera NM/CT 670 DR GE Discovery (USA) using high-resolution low-energy collimators (LEHR). The measured data were processed using specialized software Q.Brain and Q.Volumetrix MI on a Xeleris 4.0 DR workstation from GE Healthcare (USA) to obtain reconstructed axial tomographic slices. To carry out simulation computer simulation of the procedure of examination of perfusion of GM by the method of SPECT/CT has developed a software package that includes a mathematical Hoffman phantom with the ability to simulate clinical cases of hypoperfusion of different localization and size (Virtual Patient), modeling the collection of “raw” projection data and an image reconstruction program based on the OSEM algorithm (Ordered Subset Expectation Maximization). An important advantage of the mathematical modeling method is the ability to assess the quality of the reconstructed image by calculating the root-mean-square error when compared with a given phantom. In numerical experiments, the dependence of the reconstruction error on the parameters of the OSEM algorithm (on the number of subgroups – subsets, and on the number of iterations) was investigated in order to determine the conditions for achieving the best image quality. A statistical stop criterion was developed and tested. Results: For the first time, a software package was developed and tested that allows us to investigate errors in the reconstruction algorithm, which is a great difficulty when using clinical research methods. A criterion for stopping iterations is proposed when using the OSEM reconstruction algorithm – minimizing the functional deviation of the chi-square function from the target value, while the detector pixels with non-zero values are combined into blocks according to the 2×2 scheme. There is a reliable good correlation between the proposed stop criterion and the minimum of the root-mean-square error of image reconstruction. This makes it possible to introduce this criterion into the clinical practice of using computational tools for reconstructing sections of the SPECT to obtain the best image. The simulation results demonstrated the possibility of reducing the time of data recording, during which the patient must remain motionless, at least twice. Conclusion: The method of computer simulation developed in this work is a practically useful technology that helps optimize the use of SPECT to achieve the best possible results of brain imaging in patients.

Docetaxel in combination with metformin enhances antitumour efficacy in metastatic breast carcinoma models: a promising cancer targeting based on PEGylated liposomes.

Metformin has been shown to kill cancer stem-like cells in genetically various types of breast carcinoma. With the aim to simultaneously eradicate the bulk population of tumour cells and the rare population of cancer stem-like cells in breast cancer tissues, we used the combination chemotherapy of docetaxel (DTX) with metformin (MET). Furthermore, we introduce an active loading method based on ammonium sulphate 250 mM (SA) for encapsulating docetaxel into liposomes. Docetaxel and metformin encapsulated into PEGylated liposomes with two different methods based on remote or passive loading methods, respectively. The size and surface charge of the liposomes were characterized. DTX content in the nanoliposomes was measured by the high-performance liquid chromatography method. The drug release profiles were evaluated in phosphate-buffered dextrose 5% with the pH of 6.5 and 7.4. We examined the antitumour activity of Taxotere (TAX), and liposomal formulation of DTX and MET as a monotherapy or combination therapy. The biodistribution of liposomes was also investigated using 99mTc hexamethyl propylene amine oxime method in BALB/c mice bearing 4T1 breast carcinoma tumours. The final formulations were prepared according to the best physicochemical characteristics which were HSPC/mPEG2000-DSPE/Chol (DTX liposomes) and HSPC/DPPG/mPEG2000-DSPE/Chol (MET liposomes), at molar ratios of 85/5/10 and (55/5/5/35), respectively. In vivo experiments showed that when free or liposomal metformin used in combination with liposomal docetaxel, they prolonged median survival time (MST) from 31 in the control group to 46 days, which demonstrates their promising effects on the survival of the 4T1 breast carcinoma mice models. Moreover, combination therapies could significantly increase life span in comparison with phosphate-buffered saline (PBS) and Taxotere groups at the same dose. Furthermore, in the combination therapy study, treatment with DTX liposomes prepared by ammonium sulphate 250 mM buffer alone resulted in similar therapeutic efficacy to combination therapy. The biodistribution study exhibited significant accumulation of DTX liposomes in the tumours due to the Enhanced Permeability and Retention effect. This study also showed that metformin-based combinatorial chemotherapies have superior efficacy versus their corresponding monotherapy counterparts at same doses. The findings confirm that liposomes based on ammonium sulphate 250 mM could be as a promising formulation for efficient DTX delivering and cancer targeting and therefore merit further investigations.

In vivo molecular imaging stratifies rats with different susceptibilities to hyperoxic acute lung injury.

99mTc-hexamethylpropyleneamine oxime (HMPAO) and 99mTc-duramycin in vivo imaging detects pulmonary oxidative stress and cell death, respectively, in rats exposed to >95% O2 (hyperoxia) as a model of acute respiratory distress syndrome (ARDS). Preexposure to hyperoxia for 48 h followed by 24 h in room air (H-T) is protective against hyperoxia-induced lung injury. This study's objective was to determine the ability of 99mTc-HMPAO and 99mTc-duramycin to track this protection and to elucidate underlying mechanisms. Rats were exposed to normoxia, hyperoxia for 60 h, H-T, or H-T followed by 60 h of hyperoxia (H-T + 60). Imaging was performed 20 min after intravenous injection of either 99mTc-HMPAO or 99mTc-duramycin. 99mTc-HMPAO and 99mTc-duramycin lung uptake was 200% and 167% greater (P < 0.01) in hyperoxia compared with normoxia rats, respectively. On the other hand, uptake of 99mTc-HMPAO in H-T + 60 was 24% greater (P < 0.01) than in H-T rats, but 99mTc-duramycin uptake was not significantly different (P = 0.09). Lung wet-to-dry weight ratio, pleural effusion, endothelial filtration coefficient, and histological indices all showed evidence of protection and paralleled imaging results. Additional results indicate higher mitochondrial complex IV activity in H-T versus normoxia rats, suggesting that mitochondria of H-T lungs may be more tolerant of oxidative stress. A pattern of increasing lung uptake of 99mTc-HMPAO and 99mTc-duramycin correlates with advancing oxidative stress and cell death and worsening injury, whereas stable or decreasing 99mTc-HMPAO and stable 99mTc-duramycin reflects hyperoxia tolerance, suggesting the potential utility of molecular imaging for identifying at-risk hosts that are more or less susceptible to progressing to ARDS.

Localization of epileptic focus in children with intractable epilepsy

Background Epilepsy is a common neurological disorder. Preoperative evaluation of intractable epileptic patients requires identification of the brain area that is responsible for generating seizure activity. The developments of functional brain imaging with positron emission tomography, single-photon emission computed tomography (SPECT), and functional magnetic resonance imaging (MRI) have ensured its clinical relevance. Aim The aim of this work was to evaluate the role of Tc-99m hexamethylpropylene amine oxime brain-perfusion SPECT and comparing it with MRI) and electroencephalogram (EEG) in the localization of epileptic focus in children with medically intractable epilepsy. Patients and Methods The study population consisted of twenty children with medically intractable epilepsy. They were subjected to complete history taking, clinical assessment, laboratory assessment, and radiological assessment, including EEG, traditional MRI, and SPECT. Results Medically intractable epilepsy is more likely to occur in children with early age of onset, high frequency of seizures per month, more reliability of febrile seizures, and having associated neurological abnormalities. It is more likely to occur in focal forms of seizures than in generalized forms. Children with focal EEG activity and focal seizures are the most likely group to have abnormal brain MRI results and abnormal cerebral perfusion in SPECT. MRI is very important in the localization of structural lesions, but SPECT in localization of functional lesions. Conclusion Interictal SPECT results were nearly the same as the MRI results.

Reduced Regional Cerebral Blood Flow Measured by 99mTc-Hexamethyl Propylene Amine Oxime Single-Photon Emission Computed Tomography in Microgravity Simulated by 5-Day Dry Immersion.

Microgravity induces a cephalad fluid shift that is responsible for cephalic venous stasis that may increase intracranial pressure (ICP) in astronauts. 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. Around 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 4days before DI and at the end of the fifth day of DI (DI5), using single-photon emission computed tomography (SPECT) with radiopharmaceutical 99mTc-hexamethyl propylene amine oxime (99mTc-HMPAO). SPECT images were processed using statistical parametric mapping (SPM12) software. At DI5, we observed a significant decrease in rCBF in 32 cortical and subcortical regions, with greater hypoperfusion in basal ganglia (right putamen peak level: z=4.71, puncorr<0.001), bilateral occipital regions (left superior occipital peak level: z=4.51, puncorr<0.001), bilateral insula (right insula peak level: 4.10, puncorr<0.001), and bilateral inferior temporal (right inferior temporal peak level: 4.07, puncorr<0.001). No significant difference was found between the control and cuffs groups on change in rCBF after 5days of DI. After a 5-day DI, we found a decrease in rCBF in cortical and subcortical regions. However, thigh cuffs countermeasure failed to prevent hypoperfusion. To date, this is the first study measuring rCBF in DI. Further investigations are needed in order to better understand the underlying mechanisms in cerebral blood flow (CBF) changes after exposure to microgravity.

Dual-tracer approach vs. dual time-point approach in leukocyte scintigraphy in treatment evaluation of persistent chronic prosthetic joint infection.

BackgroundBoth dual time-point 99mTc-hexamethylpropylene amine oxime (HMPAO)-leukocyte scintigraphy and dual-tracer 99mTc-HMPAO-leukocyte scintigraphy (with the addition of 99mTc-nanocolloid bone marrow scintigraphy) have been used to diagnose prosthetic joint infection (PJI). A treatment evaluation of persistent PJI using these imaging protocols has yet to be presented.ObjectiveThe purpose of this study was to compare the accuracy of dual time-point 99mTc-HMPAO-leukocyte scintigraphy to the dual-tracer alternative of single time-point 99mTc-HMPAO-leukocyte scintigraphy or single-photon emission computed tomography/computed tomography (SPECT/CT) combined with a 99mTc-nanocolloid bone marrow scintigraphy or SPECT/CT, for treatment evaluation of PJI.Material and methodsThirty-one PJI patients under antibiotic treatment were included in this retrospective study. Examinations were organized into three settings. Setting one used dual time-point approach with delayed (2 h) and late (24 h) planar 99mTc-HMPAO-leukocyte scintigraphy, including both visual and semiquantitative analysis. Setting two used delayed (2 h) planar 99mTc-HMPAO-leukocyte scintigraphy combined with 99mTc-nanocolloid bone marrow scintigraphy and for setting three SPECT/CT replaced planar imaging.ResultsAccuracy was 0.68 for visual evaluation and 0.55 for semiquantitative evaluation of setting one; 0.71 for setting two; and 0.68 for setting three. Sensitivity was 0.54 for visual evaluation and 0.31 for semiquantitative evaluation of setting one; 0.38 for setting two; and 0.46 for setting three. Specificity was 0.78 for visual evaluation and 0.72 for semiquantitative evaluation of setting one; 0.94 for setting two; and 0.83 for setting three.ConclusionNo significant difference in accuracy, sensitivity, or specificity between the approaches for treatment evaluation of suspected persistent PJI in the hip or knee was observed.

Age, BMI and diabetes as independent predictors of brain hypoperfusion.

Cerebral blood flow abnormalities are supposed to be potential risk factors for developing cognitive dysfunction in the general population. Aging, obesity and type 2 diabetes mellitus are associated with perfusion abnormalities leading to cognitive impairment, neurodegeneration and future development of dementia. In our study, we aimed at identifying independent factors that contribute to the appearance of regional brain perfusion changes besides those that are already known. Forty-three type 2 diabetic and twenty-six obese patients were enrolled. After the intravenous administration of 740 MBq 99mTc-hexamethylpropylene amine oxime (HMPAO), all subjects underwent brain perfusion SPECT imaging applying AnyScan S Flex dual-head gamma camera (Mediso, Hungary). Using Philips Achieva 3T scanner brain resting-state functional MRI was also performed. The SPECT and MRI images were co-registered and transformed to the MNI152 atlas space so that data of the following standard volumes of interest (VOIs) could be obtained: frontal lobe, parietal lobe, temporal lobe, occipital lobe, limbic region, cingulate, insula, basal ganglia, cerebrum, limbic system and brain stem. Using the SPSS 25 statistical software package, general linear regression analysis, Student's t-test, and Mann-Whitney U-test were applied for statistical analyses. Multivariate linear analysis identified that BMI and age are significantly (p < 0.0001) associated with perfusion, and patient group was slightly above threshold (p = 0.0524). We also found that the presence of diabetes was an independent significant predictor of normalized regional brain perfusion only in the insula (p < 0.001). Other independent predictors of normalized regional brain perfusion were: age in the insula (p < 0.001) and in the limbic region (p < 0.01), and BMI in the brain stem (p < 0.01). Age and BMI proved to be general, and diabetes regional predictor of brain hypoperfusion. BMI appeared to be a novel factor affecting brain perfusion. In one specific region, the insula, we detected a difference between the obese and the diabetic group. These findings may be significant in the understanding of the development of cognitive impairment in metabolic diseases.

Initial results of the use of a novel semiquantitative parameter in three-phase bone scan to predict 99mTc-HMPAO-labeled leukocyte scintigraphy in patients with unilateral total knee replacement.

The aim of the study was to predict the results of 99mTc-hexamethylpropyleneamine oxime (HMPAO)-labeled autologous leukocytes scintigraphy assessing count ratios in the perfusion (Pr) and blood-pool (BPr) phase images in three-phase bone scan (3PBSr) between the prosthetic knee and the 'healthy' knee and a novel semiquantitative parameter (P/BP ratio) in patients with unilateral knee arthroplasty. Patients with unilateral knee arthroplasty and available 3PBS and 99mTc-HMPAO-labeled autologous leukocytes scintigraphic images were searched in two hospitals (A and B). In center A, the perfusion phase was not available. Regions of interest (ROI) were delineated in the perfusion (P) and blood-pool (BP) phase images, incorporating the prosthetic region and applying an isocontour (40% of the maximum pixel activity); corresponding mirror ROIs were placed on the healthy knee. The P/BP ratio was calculated as {[(Pr/BPr) × 100] - 100}. Receiver operator curves (ROCs) were generated for each semiquantitative parameter to identify the optimal cutoff for predicting the results of the autologous leukocytes scintigraphy. In the whole group (79 patients), BPr demonstrated an area under the curve (AUC) of 0.722 (optimal cutoff = 1.43). In center A (52 patients), BPr demonstrated an AUC of 0.737 (cutoff = 1.43), whereas, in center B (27 patients), AUC for BPr was 0.718 (cutoff = 1.6). A better diagnostic performance was obtained selecting Pr (AUC = 0.918; cutoff = 2.34) and P/BP ratio (AUC = 0.947; cutoff = 26.5%) for the discrimination between septic and aseptic loosening. The novel P/BP ratio seems to be a promising semiquantitative parameter to predict septic loosening. These findings warrant confirmation in larger patient samples.

Multimodal evaluation of the cerebrovascular reserve in Neurofibromatosis type 1 patients with Moyamoya syndrome

PurposeMoyamoya syndrome (MMS) is a rare intracranial arterial vasculopathy which can occur in neurofibromatosis type 1 (NF1) disease, representing a cause of cerebrovascular reserve (CVR) impairment, possibly leading to ischemic stroke. Here, we evaluated noninvasive imaging techniques used to assess CVR in MMS patients, describing clinical and imaging findings in patients affected by MMS-NF1.MethodsFollowing strict inclusion and exclusion criteria, in this retrospective observational study, we evaluated imaging data of nine consecutive MMS-NF1 patients (M/F = 5/4, mean age: 12.6 ± 4.0). Subjects underwent a multimodal evaluation of cerebral vascular status, including intracranial arterial MR Angiography (MRA), MRI perfusion with dynamic susceptibility contrast (DSC) technique, and 99mTc-hexamethylpropyleneamine oxime (HMPAO) SPECT.ResultsIn 8 out 9 patients (88.8%, 6/8 symptomatic), time-to-peak maps were correlated with the involved cerebral hemisphere, while in 6 out 9 patients (66.6%, 5/6 symptomatic), mean transit time (MTT) maps showed correspondence with the affected cerebrovascular territories. Cerebral blood flow (CBF) calculated using DSC perfusion failed to detect the hypoperfused regions instead identified by SPECT-CBF in all patients, while MTT maps overlapped with SPECT-CBF data in all cases and time-to-peak maps in 60.0%.ConclusionsAlthough SPECT imaging still represents the gold standard for CBF assessment, our results suggest that data obtained using DSC perfusion technique, and in particular MTT maps, might be a very useful and noninvasive tool for evaluating hemodynamic status in MMS-NF1 patients.

Internal Carotid Artery Test Balloon Occlusion Using Single Photon Emission Computed Tomography Scan in the Management of Complex Cerebral Aneurysms and Skull Base Tumors: A 20-Year Review

Test balloon occlusion (TBO) is important in the management of complex cerebrovascular and skull base lesions when permanent occlusion (PO) of a parent artery may be indicated. Several adjuncts may be used to increase the sensitivity of TBO to predict whether PO will be tolerated. This is an observational study to evaluate the utility of internal carotid artery (ICA) TBO using single photon emission computed tomography (SPECT) scan in the management of complex vascular pathology and skull base tumors. All TBO procedures performed over a 20-year period were analyzed. Clinical assessment and angiographic collateral flow were combined with semi-quantitative cerebral blood flow analysis using 99mTc hexamethylpropylene-amine oxime SPECT scan during ICA TBO. Evaluation of collateral circulation after TBO, and the complications of TBO and the safety of PO after successful TBO were evaluated. Eighty-three patients underwent TBO without complication. Of 45 patients with satisfactory TBO, 28 proceeded to PO. Three patients developed transient ischemic symptoms thought to be embolic in origin. Thirty-eight patients had unsatisfactory TBO, of whom 15 required PO accompanied by a bypass procedure. Forty patients in the series did not undergo permanent vessel occlusion. SPECT scan-enhanced TBO is an important component of the management of complex vascular pathology and skull base tumors, permitting safe PO of the parent vessel and definitive treatment of the main pathology.

Usefulness of HMPAO-SPECT in the diagnosis of nonconvulsive status epilepticus

BackgroundThe diagnosis of nonconvulsive status epilepticus (NCSE) can pose a challenge. Electroencephalogram (EEG) patterns can be difficult to interpret, and the absence of an EEG correlate does not rule out the diagnosis of NCSE. In this setting, neuroimaging tools to help in the diagnosis are crucial. Our aim was to evaluate the role of 99mTc-hexamethyl propyleneamine oxime (HMPAO) single photon emission computed tomography (SPECT) and quantitative HMPAO-SPECT (QtSPECT) in patients with clinical suspicion of NCSE, and to evaluate their value in the final diagnosis of NCSE. MethodsWe recruited consecutive patients admitted in our center with suspicion of NCSE, and selected those who underwent an HMPAO-SPECT. All patients were admitted to the neurology ward and underwent an EEG. We divided the patients into those who were finally with diagnosed NCSE (NCSE-p) and those who were not (non-NCSE) according to the Salzburg Diagnostic EEG criteria. Sensitivity and specificity of the diagnostic tools were calculated. The SPECTs were acquired in a Skylight SPECT (Philips Healthcare, Amsterdam). The injections were done during the clinical episode suspected of being an NCSE. The HMPAO-SPECT was analyzed by two experts and was also quantified. All data were normalized to the SPM SPECT template. We used an external healthy normal database to obtain a Z-score map for each individual versus the normal database. The Z-score maximum (Zmax) was extracted from each region of the AAL atlas as was the percentage of voxels with a Z-score higher than 2.5 (N(%)). A logistic regression combining the Zmax, N(%), and the effect of patient age was fitted to predict the final NCSE diagnosis. A receiver operator characteristic (ROC) curve and the area under the curve (AUC) were obtained to evaluate the classification performance. ResultsWe included 55 patients, 21 of them women (38.9%), with a median age of 62.1 years old (range 25–84). Thirty-six patients were with diagnosed NCSE (62.9%). Initial EEG had a sensitivity of 61.1% and a specificity of 89%. Most of the patients were critically ill with diagnostic difficulties, and it could be one of the main reasons to find low sensitivity of the Salzburg diagnostic EEG criteria. The Zmax and N(%) were significantly higher in NCSE-p than in non-NCSE (p = 0.005 and p < 0.001, respectively). The HMPAO-SPECT qualitative analysis had a sensitivity of 80.5% and specificity of 89.5% while QtSPECT had a sensitivity of 82% and specificity of 81%. ConclusionBoth 99mTc-HMPAO-SPECT and QtSPECT can be useful in the diagnosis of NCSE.This article is part of the Special Issue “Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures”

Efficacy of NMDA receptor antagonist on regional cerebral blood flow in Parkinson's disease with dementia

Although the treatment efficacy of memantine in Parkinson’s disease dementia (PDD) has been reported after several weeks of administration, the long-term effects on brain perfusion and clinical symptoms remain unclear. The current study aimed to follow-up PDD patients after 18 months of memantine treatment using 99mTc hexamethylpropylene amine oxime single photon emission computed tomography (SPECT). A total of 15 patients with PDD and 11 healthy participants were recruited into this study and they were assessed with brain SPECT, Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), Global Deterioration Scale (GDS), and Neuropsychiatric Inventory (NPI). Differences in regional cerebral blood flow (rCBF) between the two groups were evaluated at baseline. After 18 months of memantine administration, changes in brain perfusion, severity of dementia, cognition, and neuropsychiatric disturbances were examined in the patients with PDD. The PDD group showed hypoperfusion in most of the cortical, subcortical, and cerebellar areas compared to healthy controls at baseline. At the follow-up, changes in rCBF, CDR (p = 0.32), sum of box of CDR (p = 0.49), MMSE (p = 0.61), GDS (p = 0.79), and NPI (p = 0.23) were not significant in the PDD patients. Our findings implicate that memantine may delay the progression of brain perfusion deficits and clinical symptoms of PDD in the long term.

Urinary ketone body loss leads to degeneration of brain white matter in elderly SLC5A8-deficient mice

SLC5A8 is a sodium-coupled monocarboxylate and ketone transporter expressed in various epithelial cells. A putative role of SLC5A8 in neuroenergetics has been also hypothesized. To clarify this issue, we studied the cerebral phenotype of SLC5A8-deficient mice during aging. Elderly SLC5A8-deficient mice presented diffuse leukoencephalopathy characterized by intramyelinic oedema without demyelination suggesting chronic energetic crisis. Hypo-metabolism in the white matter of elderly SLC5A8-deficient mice was found using 99mTc-hexamethylpropyleneamine oxime (HMPAO) single-photon emission CT (SPECT). Since the SLC5A8 protein could not be detected in the mouse brain, it was hypothesized that the leukoencephalopathy of aging SLC5A8-deficient mice was caused by the absence of slc5a8 expression in a peripheral organ, i.e. the kidney, where SLC5A8 is strongly expressed. A hyper-excretion of the ketone β-hydroxybutyrate (BHB) in the urine of SLC5A8-deficient mice was observed and showed that SLC5A8-deficient mice suffered a cerebral BHB insufficiency. Elderly SLC5A8-deficient mice also presented altered glucose metabolism. We propose that the continuous renal loss of BHB leads to a chronic energetic deficiency in the brain of elderly SLC5A8-deficient mice who are unable to counterbalance their glucose deficit. This study highlights the importance of alternative energetic substrates in neuroenergetics especially under conditions of restricted glucose availability.

The clinical contribution of SPECT/CT with 99mTc-HMPAO-labeled leukocyte scintigraphy in hip and knee prosthetic infections.

White blood cell scanning with 99mTc-hexamethylpropylene amine oxime (HMPAO) has proven a sensitive and specific imaging method in the diagnosis of suspected prosthesis infection. The aim of this retrospective study was to evaluate the usefulness of SPECT/CT performed simultaneously using a hybrid imaging device of prosthesis infections. 99mTc-HMPAO scintigraphy was performed on 37 patients (11 men and 26 women; age range 38-84 years; mean age±SD, 65.7±5.6 years). Planar scans were acquired 2.4 and 24hour after injection. SPECT/CT was obtained 4 h after injection, using a dual-head hybrid gama camera coupled with a low-power x-ray tube. In all patients, scintigraphic results were matched with the results of surgery, cultures and clinical follow-up. Seventeen (45,9%) out of 37 patients had prosthesis infection and 20 (54,1%) out of 37 patients had non-infectious prosthesis pathologies with 99mTc-HMPAO scintigraphy and SPECT/CT. The 99mTc-HMPAO scintigraphy was true-positive for infection in 16 of 37 patients and true-negative in 20 of 37 patients. SPECT/CT provided an accurate anatomic localization of all positive foci. With regard to the final diagnosis, SPECT/CT added a significant clinical contribution in 22 of 37 patients (59,4%). Sensitivity, specificity, negative predictive value and positive predictive values were 100%,59.1%,100%,62.5% in planar images with 99mTc-HMPAO scintigraphy and 100%,90.1%,100%,88.2% in the planar+SPECT/CT imaging, respectively. Our results indicate that SPECT/CT performed using a hybrid device can improve imaging with 99mTc-HMPAO scintigraphy in patients with suspected osteomyelitis by providing accurate anatomic localization and precise definition of the extent of infection.

Neuropathological Changes in Dementia With Lewy Bodies and the Cingulate Island Sign.

The cingulate island sign (CIS) refers to the relative sparing of metabolism in the posterior cingulate cortex (PCC) and represents an important biomarker in distinguishing dementia with Lewy bodies (DLB) from Alzheimer disease (AD). The underlying basis of the CIS is unknown; therefore, our aim was to investigate which neurodegenerative changes underpin the formation of CIS. Using quantitative neuropathology, α-synuclein, phosphorylated Tau, and amyloid-β pathology was assessed in 12 DLB, 9 AD and 6 age-matched control patients in the anterior cingulate (ACC), midcingulate, PCC, precuneus/cuneus and parahippocampal gyrus. All participants had undergone 99mTc-hexamethylpropyleneamine oxime (HMPAO) single-photon emission computed tomography imaging during life to define the presence or absence of CIS. In the DLB group, no significant correlations were observed between CIS ratios and neurodegenerative pathology in PCC. In DLB, however, the ACC showed lower HMPAO uptake, as well as significantly higher α-synuclein and amyloid-β burden compared with PCC, possibly underlying the relative preservation of perfusion in PCC when compared with ACC. Our findings suggest that neurodegenerative pathology does not directly correlate with the CIS in DLB, and other metabolic or pathological changes are therefore more likely to be relevant for the development of the CIS.

The clinical contribution of SPECT/CT with 99mTc-HMPAO-labeled leukocyte scintigraphy in hip and knee prosthetic infections

ObjectivesWhite blood cell scanning with 99mTc-hexamethylpropylene amine oxime(HMPAO) has proven a sensitive and specific imaging method in the diagnosis of suspected prosthesis infection. The aim of this retrospective study was to evaluate the usefulness of SPECT/CT performed simultaneously using a hybrid imaging device of prosthesis infections. Materials and methods99mTc-HMPAO scintigraphy was performed on 37 patients (11 men and 26 women; age range 38-84 years; mean age±SD, 65.7±5.6 years). Planar scans were acquired 2.,4. and 24. hour after injection. SPECT/CT was obtained 4 h after injection, using a dual-head hybrid gama camera coupled with a low-power x-ray tube. In all patients, scintigraphic results were matched with the results of surgery, cultures and clinical follow-up. ResultsSeventeen (45,9%) out of 37 patients had prosthesis infection and 20 (54,1%) out of 37 patients had non-infectious prosthesis pathologies with 99mTc-HMPAO scintigraphy and SPECT/CT. The 99mTc-HMPAO scintigraphy was true-positive for infection in 16 of 37 patients and true-negative in 20 of 37 patients. SPECT/CT provided an accurate anatomic localization of all positive foci. With regard to the final diagnosis, SPECT/CT added a significant clinical contribution in 22 of 37 patients(59,4%). Sensitivity, specificity, negative predictive value(NPD) and positive predictive values(PPD) were 100%,59.1%,100%,62.5% in planar images with 99mTc-HMPAO scintigraphy and 100%,90.1%,100%,88.2% in the planar+SPECT/CT imaging, respectively. ConclusionOur results indicate that SPECT/CT performed using a hybrid device can improve imaging with 99mTc-HMPAO scintigraphy in patients with suspected osteomyelitis by providing accurate anatomic localization and precise definition of the extent of infection.

The long-term effects of single and repeated subanaesthetic ketamine administration on regional cerebral blood flow in healthy dogs measured with 99mTc-HMPAO SPECT

Subanaesthetic ketamine has recently been established as an effective and rapid treatment for major depressive disorder showing antidepressant effects for up to 1 week on average. The use of repeated ketamine infusions has been put forward to augment and to prolong the antidepressant response and increase the remission rates. The underlying neurobiological mechanisms responsible for ketamine's antidepressant effects remain unclear. Nevertheless, it has been shown, both in dogs and humans, that ketamine can alter neuronal perfusion and therefore neuronal function in brain regions involved in psychiatric and behavioural disorders. Consequently, the aim of the current placebo controlled study was to assess the long-term effects on cerebral perfusion of single and repeated subanaesthetic ketamine infusions in dogs. Twelve healthy, laboratory dogs were scanned at six different time points following single and repeated ketamine administration, using Single Photon Emission Computed Tomography with the radiotracer 99mTc-hexamethylpropylene amine oxime. We hypothesised that repeated infusions could lead to more prolonged perfusion alterations in brain regions critical for behaviour regulation. We found that repeated subanaesthetic ketamine administration did not result in more prolonged cerebral perfusion alterations compared to a single ketamine administration.

The influence of subanaesthetic ketamine on regional cerebral blood flow in healthy dogs measured with 99mTc-HMPAO SPECT.

Subanaesthetic ketamine has recently been proven to be a highly effective and fast acting alternative treatment for several psychiatric disorders. The mechanisms responsible for ketamine’s antidepressant effects remain unclear, but a possible explanation could be that ketamine interacts with regional cerebral blood flow (rCBF). Therefore, the effects of two subanaesthetic ketamine doses on rCBF were evaluated. Twelve dogs were randomly assigned to one of the three treatment conditions (condition saline, condition 0.5 mg/kg ketamine or condition 2 mg/kg ketamine) and received in total five saline or ketamine infusions, with one week interval. Single Photon Emission Computed Tomography (SPECT) scans with the radiotracer 99mTc-hexamethylpropylene amine oxime were performed before the start of the infusions (baseline) and 24 hours after the first (single) and last (multiple) infusion. After a wash out period of 3 months, the animals were again assigned to one of the three treatment conditions described above and the infusion/scan protocol was repeated. During the infusions, cardiovascular parameters were evaluated every ten minutes. A one-way repeated measure ANOVA was set up to assess perfusion index for each ketamine dose for the left frontal cortex (alpha = 0.05). The remaining 11 brain regions were post hoc assessed. Perfusion index was significantly increased in the left frontal cortex and in the thalamus 24 hours after single and multiple ketamine infusions compared to baseline in the 2 mg/kg condition. No clinically relevant cardiovascular effects were observed during the ketamine infusions. This study shows that subanaesthetic ketamine can increase neuronal perfusion and therefore alter neuronal function in brain regions involved in depression and anxiety disorders. These perfusion increases may possibly contribute to ketamine’s beneficial effects in these psychiatric disorders.

A new model of experimental hemispherotomy in young adult Rattus norvegicus: a neural tract tracing and SPECT in vivo study.

The objective of this study was to describe a new experimental model of hemispherotomy performed on laboratory animals. Twenty-six male young adult Wistar rats were distributed into two groups (surgery and control). The nonfluorescent anterograde neurotracer biotinylated dextran amine (BDA; 10,000 MW) was microinjected into the motor cortex area (M1) according to The Rat Brain in Stereotaxic Coordinates atlas to identify pathways and fibers disconnected after the experimental hemispherectomy. SPECT tomographic images of 99mTc hexamethylpropyleneamine oxime were obtained to verify perfusion in functioning areas of the disconnected and intact brain. A reproducible and validated surgical procedure is described in detail, including exact measurements and anatomical relationships. An additional 30 rodents (n = 10 rats per group) were divided into naïve, sham, and hemispherotomy groups and underwent the rotarod test. Cortico-cortical neural pathways were identified crossing the midline and contacting neuronal perikarya in the contralateral brain hemisphere in controls, but not in animals undergoing hemispherotomy. There was an absence of perfusion in the left side of the brain of the animals undergoing hemispherotomy. Motor performance was significantly affected by brain injuries, increasing the number of attempts to maintain balance on the moving cylinder in the rotarod test at 10 and 30 days after the hemispherotomy, with a tendency to minimize the motor performance deficit over time. The present findings show that the technique reproduced neural disconnection with minimal resection of brain parenchyma in young adult rats, thereby duplicating the hemispherotomy procedures in human patients.