HMPAO Research Articles

The possible connection between neutrophil-to-high-density lipoprotein ratio and cerebral perfusion in clinically established corticobasal syndrome: a pilot study.

Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) are tauopathic atypical parkinsonisms. Given their overlap in terms of clinical manifestation, there is growing interest in the mechanisms leading to these entities. In total, 71 patients were included in the study, 19 of whom were clinically diagnosed with CBS, 37 with PSP, and 15 with Parkinson's disease (PD). The mean ages of the participants were 72.8, 72.9, and 64.0 years, respectively, and the disease duration varied from 3 to 6 years. Each individual underwent blood collection. Morphological and biochemical evaluation of blood samples was performed to analyze the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-high-density lipoprotein ratio (NHR). A single-photon emission computed tomography (SPECT) with technetium-99m hexamethylpropyleneamine oxime (99Tc-HMPAO) tracer was used to assess perfusion in two regions of interest (ROI): the thalamus and insula. Using Pearson correlation to assess the linear relationship between NHR and perfusion in the insula and thalamus for CBS, PSP, and PD patients, the authors intended to verify possible correlations between NLR, PLR, and NHR and perfusion in the indicated ROIs. The study revealed a negative linear correlation between NHR and perfusion of both the left (Insula L; R = -0.59) and right (Insula R; R = -0.58) insula regions. Similar to the insula, a linear correlation between NHR and activity in both the left (Thalamus L) and right (Thalamus R) thalamus regions in CBS subjects with a relatively stronger correlation in the right thalamus (R = -0.64 vs. R = -0.58) was found. These observations were not confirmed in PSP and PD patients. Simultaneously using non-specific parameters for peripheral inflammation (NLR, PLR, and NHR) and perfusion, SPECT may be an interesting beginning point for further analysis of inflammatory disease mechanisms. To the best of our knowledge, this is the first study to address the potential correlation between the peripheral neuroinflammatory markers NLR, PLR, and NHR and perfusion disturbances in particular ROIs.

C-peptide: an essential ally in microvascular complications of type 2 diabetes mellitus and obesity

BackgroundIn order to investigate microvascular complications in metabolic diseases, we aimed to investigate cerebral and peripheral microcirculation in relation to peripheral neuropathy and laboratory biomarkers in type 2 diabetes mellitus (T2DM) and obesity.MethodsBased on the degree of neuropathy (NP), study participants (40 T2DM and 30 obese individuals) were classified into no-NP, mild-NP and severe-NP subgroups. After the injection of Technetium-99 m hexamethylpropylene amine oxime, both T2DM and obese participants underwent single-photon emission computed tomography/computed tomography ([99mTc]Tc-HMPAO SPECT/CT) and SPECT-only examinations to assess lower limb and brain perfusion; respectively. Peripheral nerve function was evaluated with a neurometer and glycaemic markers were measured from plasma in both groups.ResultsCompared to the obese individuals, lower extremity perfusion was significantly reduced in the diabetic subjects (p < 0.005), while it showed a positive correlation with C-peptide levels and negative association with HbA1c values. A U-shape pattern of peripheral microcirculation was observed between the NP groups, indicating a surprisingly better perfusion in the severe-NP group than in the mild one, with the highest levels in obese patients. Since changes in the C-peptide levels exhibited a similar U-shaped trend across the NP subgroups, we suggest a positive correlation between C-peptide levels and the extent of peripheral perfusion. Although, C-peptide values and cerebral microcirculation correlated positively (rho = 0.27), brain perfusion did not show any differences neither between the diabetic and the obese patients, nor between the NP subgroups (at p < 0.05).ConclusionsEstablishing the link between neuropathy and peripheral microcirculation, C-peptide seems to be a promising biomarker for the prediction of microvascular alterations in metabolic diseases. Of note, the dominance of metabolic factors over microvascular damage in the development of obesity-related neuropathy should be emphasized as well.

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

Nuclear 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. Leukocytes 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. Successful [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. Although 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.

Unusual Case of Pseudomembranous Colitis Presenting as Fever of Unknown Origin Diagnosed by Tc-99m-HMPAO-labeled Leukocytes SPECT/CT.

The fever of unknown origin (FUO) represents a complex diagnostic challenge due to the wide range of etiologies that could cause it, including neoplastic, infectious, rheumatic/inflammatory, and miscellaneous disorders. Several nuclear medicine techniques have proven to be valuable tools for guiding etiologic diagnosis in the setting of FUO. One of these is technetium-99m (Tc-99m)-hexamethylpropylene amine oxime (HMPAO)-labeled leukocyte scintigraphy, which is a diagnosis method that allows in most cases the localization and evaluation of the extension of an occult infection. This paper presents an uncommon case of pseudomembranous colitis without diarrhea as etiology of FUO diagnosed by Tc-99m-HMPAO-labeled leukocytes.

Maximum isotope accumulation in the retrosplenial cortex during amnesia attack and its temporal change suggest cortical spreading depression as a pathophysiology of patients with transient global amnesia

AbstractTransient global amnesia (TGA) is a clinical syndrome that is characterized by the sudden onset of anterograde amnesia and a less prominent impairment in retrograde memory lasting up to 24 h. Although several etiologies have been proposed, including migraine, epilepsy, ischemia, venous congestion, and glutamate toxicity, none sufficiently explain the disorder in its entirety. We retrospectively investigated images obtained using single‐photon emission computed tomography (SPECT), performed with 99mtechnetium hexamethylpropyleneamine oxime, from 11 patients with TGA divided into the following groups based on the timing of SPECT: during TGA (n = 2, Group 1), at the start of the attenuation of memory impairments (n = 2, Group 2), and after TGA (n = 7, Group 3). Regional isotope accumulation was examined using a three‐dimensional stereotactic surface projection (3D‐SSP) analysis. After calculating the mathematical product of the mean severity and extent ratio, unique comparable bar graphs were prepared with respect to Brodmann's areas (B). Increases in isotope accumulation were the largest in the retrosplenial cortex (B29, B30), posterior cingulate cortex (B23, B31), and precuneus (B7) in Groups 1 and 2, whereas decreases were noted in the same regions in Group 3. This is the first study to identify cerebral sites and describe changes consistent with the completion of amnesia as a symptom using an image analysis, such as a 3D‐SSP analysis. We consider cortical spreading depression (CSD) to be the etiology of TGA based on maximum isotope accumulation in the above sites and a literature review on CSD.

Investigation of radiological properties of imaging agents used in nuclear medicine with different methods and GATE/Geant4 simulation program

This study aims to determine the radiological properties of various radiopharmaceuticals used in nuclear medicine. In the study, mass attenuation coefficient values in different energy ranges were obtained for six different radiopharmaceuticals dimercaptosuccinic acid, diethylenetriamine pentaacetate, mercaptoacetyltriglycine, hexamethylpropyleneamine oxime, methoxyisobutylisonitrile, methylene diphosphate by using GATE simulation program, XCOM and WinXCom programs. Using these values, effective atomic number and electron density values were calculated with the help of the direct method, interpolation method, Auto-Zeff software, Phy-X/ZeXTra, XMuDat program, and Mayneourd's formula. In addition, the effective atomic number and electron density values obtained were compared for each radiopharmaceutical, both among themselves and between the methods. When radiopharmaceuticals were compared among themselves in low and high-energy regions, the highest effective atomic number values were obtained in dimercaptosuccinic acid, methylene diphosphate, and mercaptoacetyltriglycine. The mass attenuation coefficient values calculated using the GATE code indicate that it is a suitable method for determining the mass attenuation coefficient for imaging agents with no experimental values. This study indicates that the simulation geometry method is suitable to be used as an alternative method for the experiments. In addition, the values obtained for these molecules used as radiopharmaceuticals were examined for the first time.

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.

Effects of cranioplasty in cerebral blood perfusion using quantification with 99m-Tc HMPAO SPECT-CT.

Syndrome of the trephined or sinking skin flap syndrome is an underdiagnosed condition of craniectomized patients that usually improves after cranioplasty. Among the pathophysiological theories proposed, the changes of cerebral blood perfusion (CBP) caused by cranial defects might have a role in the neurological deficiencies observed. We aim to assess the regional cortex changes in CBP after cranioplasty with Technetium 99m hexamethylpropylene-amine oxime (99mTc-HMPAO) SPECT-CT. Twenty-eight craniectomized patients subject to cranioplasty were studied with 99mTc-HMPAO SPECT-CT in three different times, before cranioplasty, a week, and 3months after. The images were processed with quantification software comparing CBP of 24 cortical areas with a reference area, and with a database of controls. A mixed effects model and T-Student were used. CBP increased significantly in both hemispheres after cranioplasty, either using ratio (β=.019, p-value=.030 first postsurgical SPECT-CT and β=.021, p-value=.015 in the second study, vs. presurgical) or Z-score (β=.220, p-value=.026 and β=.279, p-value=.005, respectively). Nine 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=.034) and Z-score (p-value=.028) in the first postsurgical SPECT-CT. These posterior cingulate changes represent a 4.83% increase in ratio and 91.04% in Z-Score (p-value=.035 and .040, respectively). CBP changes significantly in specific cortical areas after cranioplasty. Posterior cingulate changes might explain some improvements in attention impairments. SPECT-CT could be a useful tool to assess CBP changes in these patients and might be helpful in their clinical management.

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.

The Legacy of the TTASAAN Report - Premature Conclusions and Forgotten Promises About SPECT Neuroimaging: A Review of Policy and Practice Part II.

Brain perfusion single photon emission computed tomography (SPECT) scans were initially developed in 1970s. A key radiopharmaceutical, hexamethylpropyleneamine oxime (HMPAO), was not stabilized until 1993 and most early SPECT scans were performed on single-head gamma cameras. These early scans were of inferior quality. In 1996, the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology (TTASAAN) issued a report regarding the use of SPECT in the evaluation of neurological disorders. This two-part series explores the policies and procedures related to perfusion SPECT functional neuroimaging. In Part I, the comparison between the quality of the SPECT scans and the depth of the data for key neurological and psychiatric indications at the time of the TTASAAN report vs. the intervening 25 years were presented. In Part II, the technical aspects of perfusion SPECT neuroimaging and image processing will be explored. The role of color scales will be reviewed and the process of interpreting a SPECT scan will be presented. Interpretation of a functional brain scans requires not only anatomical knowledge, but also technical understanding on correctly performing a scan, regardless of the scanning modality. Awareness of technical limitations allows the clinician to properly interpret a functional brain scan. With this foundation, four scenarios in which perfusion SPECT neuroimaging, together with other imaging modalities and testing, lead to a narrowing of the differential diagnoses and better treatment. Lastly, recommendations for the revision of current policies and practices are made.

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.

Multimodality radionuclide imaging in fever of unknown origin presenting with a solitary spleen lesion

BackgroundFever of unknown origin (FUO) still represents a serious challenge for clinicians, since it can be related to a wide spectrum of disorders, ranging from infections to malignancies. In this scenario, nuclear medicine can be of value to achieve a correct diagnosis both through positron emission computed tomography (PET/CT) and 99mTc labeled hexamethylpropylene amine oxime (HMPAO) white blood cell (WBC) scintigraphy.Case presentationWe are presenting the case of 65-year-old male, who was referred to our hospital due to prolonged unexplained fever. He was submitted to abdomen ultrasonography (US) that did not disclose relevant pathological findings. Subsequently, he underwent PET/CT scan with 18F-fluorodeoxyglucose (18F-FDG) that revealed an area of increased tracer uptake in splenic inferior pole. In order to solve differential diagnosis between tumor and infection, he was submitted to 99mTc-HMPAO WBC scintigraphy that resulted negative for sites of pathologic radiolabeled cells’ accumulation but revealed a photopenic area in the splenic inferior pole. The pattern of mismatched uptake between 18F-FDG PET/CT and 99mTc-HMPAO WBC scintigraphy was considered highly suspicious for spleen tumor localization. The patient was scheduled for splenectomy and histology resulted positive for non-Hodgkin lymphoma (NHL) of diffuse large B cell type. After splenectomy, a further 18F-FDG PET/CT revealed the appearance of hypermetabolic hepatic lesions. The patient underwent chemotherapy with complete remission.ConclusionNuclear medicine provides valuable tools for differential diagnosis in FUO. In case of patients presenting solitary lesion of the spleen, the combined use of 18F-FDG PET/CT and 99mTc-HMPAO WBC scintigraphy can provide relevant information to aid clinicians to a correct diagnosis.

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.

The Legacy of the TTASAAN Report-Premature Conclusions and Forgotten Promises: A Review of Policy and Practice Part I.

Brain perfusion single photon emission computed tomography (SPECT) scans were initially developed in 1970's. A key radiopharmaceutical, hexamethylpropyleneamine oxime (HMPAO), was originally approved in 1988, but was unstable. As a result, the quality of SPECT images varied greatly based on technique until 1993, when a method of stabilizing HMPAO was developed. In addition, most SPECT perfusion studies pre-1996 were performed on single-head gamma cameras. In 1996, the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology (TTASAAN) issued a report regarding the use of SPECT in the evaluation of neurological disorders. Although the TTASAAN report was published in January 1996, it was approved for publication in October 1994. Consequently, the reported brain SPECT studies relied upon to derive the conclusions of the TTASAAN report largely pre-date the introduction of stabilized HMPAO. While only 12% of the studies on traumatic brain injury (TBI) in the TTASAAN report utilized stable tracers and multi-head cameras, 69 subsequent studies with more than 23,000 subjects describe the utility of perfusion SPECT scans in the evaluation of TBI. Similarly, dementia SPECT imaging has improved. Modern SPECT utilizing multi-headed gamma cameras and quantitative analysis has a sensitivity of 86% and a specificity of 89% for the diagnosis of mild to moderate Alzheimer's disease—comparable to fluorodeoxyglucose positron emission tomography. Advances also have occurred in seizure neuroimaging. Lastly, developments in SPECT imaging of neurotoxicity and neuropsychiatric disorders have been striking. At the 25-year anniversary of the publication of the TTASAAN report, it is time to re-examine the utility of perfusion SPECT brain imaging. Herein, we review studies cited by the TTASAAN report vs. current brain SPECT imaging research literature for the major indications addressed in the report, as well as for emerging indications. In Part II, we elaborate technical aspects of SPECT neuroimaging and discuss scan interpretation for the clinician.

99m Technetium-HMPAO-labeled platelet scan in practice: Preparation, quality control, and biodistribution studies

There is no biodistribution or imaging data on 99mtechnetium (Tc)-hexamethyl propylamine oxime (HMPAO)-labeled platelets in the literature. The current study aimed to present updated information about the clinical procedures for preparation and use of labeled platelets. Following two-step centrifugation at 1500 and 2500 rpm, the platelets were extracted from whole blood into platelet-rich plasma (PRP) above the buffy coat and then from PRP into a platelet pellet at the bottom of the tube. The 99mTc-HMPAO-labeled platelets were inspected for purity, viability, release of 99mTc from platelets, and sterility. Also, microscopic examination and thin layer chromatography (TLC) were performed. Biodistribution was assessed following necropsy in BALB/c mice and through imaging of New Zealand rabbits. The separation ratio was estimated at 98%, and radiochemical purity was measured to be 80%. The labeling efficiency was above 30% in more than half of the assays (range: 17-43%). The release of 99mTc from platelets was 9% per hour at 37ºC. After 24 hours, stability was estimated at 54% in the human serum. The target organs of mice included the spleen and liver. In rabbits, the imaging results indicated liver as the target organ. Thyroid uptake was negligible up to 90 minutes. Based on the findings, extraction of platelets and labeling them with 99mTc-HMPAO is a feasible and safe approach in routine practice.

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.

Unexpected Detection of Abscessualized Lung Carcinoma on Tc-99m-HMPAO-labeled Leukocytes Scintigraphy Misdiagnosed on Chest Computed Tomography.

Technetium-99m (Tc-99m)-hexamethylpropylene amine oxime (HMPAO)-labeled leukocytes scintigraphy is well established for investigating and diagnosing infections in bone and soft tissue, as well as for the detection of occult infection. A 71-year-old female who was recently diagnosed with bronchopulmonary neuroendocrine tumor of the right lung was referred for an intermittent fever of unknown origin associated with chill at night for the last month. Chest computed tomography (CT) scan showed a thrombotic widespread of the superior vena cava and a solid pathological tissue in the superior segment of the inferior lobe of the right lung with consensual atelectasis. Being a carrier of port-a-cath, an infection of this device was suspected. Therefore, Tc-99m-HMPAO-labeled leukocytes single-photon emission computed tomography (SPECT) was performed, and matching pairs of CT scan and Tc-99m-HMPAO-labeled white blood cell SPECT images were fused. Through this means, it was found that the area of the radiotracer increased uptake corresponded with the soft tissue density mass detected by CT scan localized at the inferior lobe of the right lung. The hybrid SPECT/CT fused imaging was crucial for diagnosis of the presence of a lung abscess localized in correspondence with the known lung cancer region.

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.

PET Detection of Cerebral Necrosis Using an Infarct-Avid Agent 2-Deoxy-2-[18F]Fluoro-D-Glucaric Acid (FGA) in a Mouse Model of the Brain Stroke.

Ischemic stroke is a leading cause of disability worldwide. The volume of necrotic core in affected tissue plays a major role in selecting stroke patients for thrombolytic therapy or endovascular thrombectomy. In this study, we investigated a recently reported positron emission tomography (PET) agent 2-deoxy-2-[18F]fluoro-D-glucaric acid (FGA) to determine necrotic core in a model of transient middle cerebral artery occlusion (t-MCAO) in mice. The radiopharmaceutical, FGA, was synthesized by controlled, rapid, and quantitative oxidation of clinical doses of 2-deoxy-2-[18F]fluoro-D-glucose (FDG) in a one-step reaction using a premade kit. Brain stroke was induced in the left cerebral hemisphere of CD-1 mice by occluding the middle cerebral artery for 1h, and then allowing reperfusion by removing the occlusion. One day post-ictus, perfusion single-photon emission tomography (SPECT) was performed with 99mTc-lableled hexamethylpropyleneamine oxime (HMPAO), followed by PET acquisition with FGA. Plasma and brain tissue homogenates were assayed for markers of inflammation and neurotrophins. The kit-based synthesis was able to convert up to 2.2GBq of FDG into FGA within 5min. PET images showed 375% more accumulation of FGA in the ipsilateral hemisphere than in the contralateral hemisphere. SPECT images showed that the ipsilateral HMPAO accumulation was reduced to 55% of normal levels; there was a significant negative correlation between the ipsilateral accumulation of FGA and HMAPO (p < 0.05). FGA accumulation in stroke also correlated with IL-6 levels in the ipsilateral hemisphere. There was no change in IL-6 or TNFα in the plasma of stroke mice. Accumulation of FGA correlated well with the perfusion defect and inflammatory injury. As a PET agent, FGA has potential to image infarcted core in the brain stroke injury with high sensitivity, resolution, and specificity.