Dopamine Transporter SPECT Imaging Research Articles

Practical use of DAT SPECT imaging in diagnosing dementia with Lewy bodies: a US perspective of current guidelines and future directions.

Diagnosing Dementia with Lewy Bodies (DLB) remains a challenge in clinical practice. The use of 123I-ioflupane (DaTscan™) SPECT imaging, which detects reduced dopamine transporter (DAT) uptake-a key biomarker in DLB diagnosis-could improve diagnostic accuracy. However, DAT imaging is underutilized despite its potential, contributing to delays and suboptimal patient management. This review evaluates DLB diagnostic practices and challenges faced within the U.S. by synthesizing information from current literature, consensus guidelines, expert opinions, and recent updates on DaTscan FDA filings. It contrasts DAT SPECT with alternative biomarkers, provides recommendations for when DAT SPECT imaging may be indicated and discusses the potential of emerging biomarkers in enhancing diagnostic approaches. The radiopharmaceutical 123I-ioflupane for SPECT imaging was initially approved in Europe (2000) and later in the US (2011) for Parkinsonism/Essential Tremor. Its application was extended in 2022 to include the diagnosis of DLB. DaTscan's diagnostic efficacy for DLB, with its sensitivity, specificity, and predictive values, confirms its clinical utility. However, US implementation faces challenges such as insurance barriers, costs, access issues, and regional availability disparities. 123I-ioflupane SPECT Imaging is indicated for DLB diagnosis and differential diagnosis of Alzheimer's Disease, particularly in uncertain cases. Addressing diagnostic obstacles and enhancing physician-patient education could improve and expedite DLB diagnosis. Collaborative efforts among neurologists, geriatric psychiatrists, psychologists, and memory clinic staff are key to increasing diagnostic accuracy and care in DLB management.

Evaluation of Collimators in a High-Resolution, Whole-Body SPECT/CT Device with a Dual-Head Cadmium-Zinc-Telluride Detector for 123I-FP-CIT SPECT.

The study aim was to evaluate the adaptation of collimators to 123I-N-fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl)nortropane (123I-FP-CIT) dopamine transporter SPECT (DAT-SPECT) by a high-resolution whole-body SPECT/CT system with a cadmium-zinc-telluride detector (C-SPECT) in terms of image quality, quantitation, diagnostic performance, and acquisition time. Methods: Using a C-SPECT device equipped with a wide-energy, high-resolution collimator and a medium-energy, high-resolution sensitivity (MEHRS) collimator, we evaluated the image quality and quantification of DAT-SPECT for an anthropomorphic striatal phantom. Ordered-subset expectation maximization iterative reconstruction with resolution recovery, scatter, and attenuation correction was used, and the optimal collimator was determined on the basis of the contrast-to-noise ratio (CNR), percentage contrast, and specific binding ratio. The acquisition time that could be reduced using the optimal collimator was determined. The optimal collimator was used to retrospectively evaluate diagnostic accuracy via receiver-operating-characteristic analysis and specific binding ratios for 41 consecutive patients who underwent DAT-SPECT. Results: When the collimators were compared in the phantom verification, the CNR and percentage contrast were significantly higher for the MEHRS collimator than for the wide-energy high-resolution collimator (P < 0.05). There was no significant difference in the CNR between 30 and 15 min of imaging time using the MEHRS collimator. In the clinical study, the areas under the curve for acquisition times of 30 and 15 min were 0.927 and 0.906, respectively, and the diagnostic accuracies of the DAT-SPECT images did not significantly differ between the 2 times. Conclusion: The MEHRS collimator provided the best results for DAT-SPECT with C-SPECT; shorter acquisition times (<15 min) may be possible with injected activity of 167-186 MBq.

Dopamine transporter SPECT imaging in Parkinson's disease and atypical Parkinsonism: a study of 137 patients.

Differential diagnosis between Parkinson's disease (PD) and multiple system atrophy-parkinsonian type (MSA-P), corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP), collectively termed atypical Parkinsonism (AP), is challenging. Dopamine transporter density imaging with Ioflupane I123 (DaTscan) is a marker of presynaptic nigrostriatal dysfunction. The primary aim of this study was to investigate the utility of DaTscan in the differential diagnosis of MSA-P, CBD, and PSP. Patients examined at Eginition Hospital (2011-2021), with available DaTscan data and a diagnosis of probable AP, clinically established PD, as well as a neurological control (NC) group were included. Mean binding specific index (BSI), BSI of the most affected side, asymmetry index, laterality, and caudate/putamen ratio were recorded. Analyses were performed by Kruskal-Wallis and ANCOVA. 137 patients were included (CBD: [Formula: see text]; MSA-P: [Formula: see text]; PSP: [Formula: see text]; PD: [Formula: see text]; NC: [Formula: see text]). There were significant differences when comparing CBS, PSP, and NC vs. all other groups combined. Pairwise between-group comparisons revealed significant differences between PSP and CBD (mean striatum BSI>1.95; sensitivity 74.1%; specificity 85.0%), CBD and MSA-P (mean striatum BSI>2.04; sensitivity 70.4%; specificity 86.7%), and CBD and PD (mean striatum BSI>2.11; sensitivity 66.7%; specificity 100.0%). There were no differences between PSP, MSA-P, and PD. PSP, MSA-P, and PD differed from NC subjects, with 100% specificity and high sensitivity. Differentiation of NC from CBD was suboptimal. CBD patients exhibit relatively mild DaTscan abnormalities. DaTscan may assist in the differentiation of CBD from PSP. DaTscan does not differentiate among PD, MSA-P, and PSP.

Diagnostic value of micrographia in Parkinson’s disease: a study with [123I]FP-CIT SPECT

Micrographia is a common symptom of Parkinson’s disease (PD), and it may precede other motor symptoms. Despite the high prevalence of micrographia in PD, its neurobiological mechanisms are not known. Given that levodopa may alleviate consistent micrographia and that nondopaminergic essential tremor (ET) is not associated with micrographia, micrographia could possibly be used as an ancillary diagnostic method that reflects nigrostriatal dopamine function. We evaluated the usefulness of micrographia as a simple one-sentence writing test in differentiating PD from ET. A total of 146 PD patients, 42 ET patients and 38 healthy controls provided writing samples and were scanned with brain [123I]FP-CIT dopamine transporter (DAT) SPECT imaging with ROI-based and voxelwise analyses. The diagnostic accuracy of micrographia was evaluated and compared to that of DAT binding. Compared to ET and healthy controls, PD patients showed micrographia (consistent, 25.6% smaller area of handwriting sample in PD compared to ET, p = 0.002, and 27.2% smaller area of handwriting compared to healthy controls, p = 0.004). PD patients showed 133% more severe progressive micrographia compared with ET patients (median b = − 0.14 in PD, b = − 0.06 in ET, p = 0.021). In early unmedicated cognitively normal patients, consistent micrographia showed 71.2% specificity and 87.5% sensitivity in PD versus ET differentiation, but micrographia had no correlation with striatal or extrastriatal [123I]FP-CIT binding in patients with PD. The one-sentence micrographia test shows moderately good accuracy in PD versus ET differentiation. The severity of micrographia has no relationship with DAT binding, suggesting nondopaminergic mechanism of micrographia in PD.ClinicalTrials.gov identifier: NCT02650843 (NMDAT study).

Dopamine transporter SPECT imaging in corticobasal syndrome: A peak into the underlying pathology?

Multiple pathologies may underlie corticobasal syndrome (CBS), including Alzheimer's disease (AD). Dopamine transporter density imaging with Ioflupane 123 I SPECT (DaTscan) may be normal in CBS. No studies to date have examined the relationship between DaTscan status and underlying pathology in CBS. The main objective of the study was to test whether a normal DaTscan in CBS patients is indicative of an underlying AD pathology, as determined by cerebrospinal fluid (CSF) biomarkers. Eighteen CBS patients were included. They were divided into patients with an AD and a non-AD disease pathology, based on their cerebrospinal fluid biochemical profile. A typical AD CSF profile was defined as an increase in total and phosphorylated at threonine 181 tau protein in addition to a decrease in amyloid-beta with 42 amino acids. DaTscan data were compared in these two groups. Eight of the 18 CBS patients (44%) had a normal DaTscan. Seven of the 18 CBS patients (39%) had an AD cerebrospinal fluid biochemical profile. Two of seven CBS patients with AD biomarker profile had abnormal DaTscans. Three of 11 CBS patients with a non-AD biomarker profile had normal DaTscans. A normal DaTscan was indicative of AD pathology with suboptimal (~70%) sensitivity and specificity. Semi-quantitative DaTscan analysis did not differentiate between AD from non-AD CSF biomarker profile in CBS. A normal DaTscan is indicative of AD in CBS, but the sensitivity and specificity of DaTscan as an in vivo marker of AD pathology is suboptimal.

Explainable AI to improve acceptance of convolutional neural networks for automatic classification of dopamine transporter SPECT in the diagnosis of clinically uncertain parkinsonian syndromes

PurposeDeep convolutional neural networks (CNN) provide high accuracy for automatic classification of dopamine transporter (DAT) SPECT images. However, CNN are inherently black-box in nature lacking any kind of explanation for their decisions. This limits their acceptance for clinical use. This study tested layer-wise relevance propagation (LRP) to explain CNN-based classification of DAT-SPECT in patients with clinically uncertain parkinsonian syndromes.MethodsThe study retrospectively included 1296 clinical DAT-SPECT with visual binary interpretation as “normal” or “reduced” by two experienced readers as standard-of-truth. A custom-made CNN was trained with 1008 randomly selected DAT-SPECT. The remaining 288 DAT-SPECT were used to assess classification performance of the CNN and to test LRP for explanation of the CNN-based classification.ResultsOverall accuracy, sensitivity, and specificity of the CNN were 95.8%, 92.8%, and 98.7%, respectively. LRP provided relevance maps that were easy to interpret in each individual DAT-SPECT. In particular, the putamen in the hemisphere most affected by nigrostriatal degeneration was the most relevant brain region for CNN-based classification in all reduced DAT-SPECT. Some misclassified DAT-SPECT showed an “inconsistent” relevance map more typical for the true class label.ConclusionLRP is useful to provide explanation of CNN-based decisions in individual DAT-SPECT and, therefore, can be recommended to support CNN-based classification of DAT-SPECT in clinical routine. Total computation time of 3 s is compatible with busy clinical workflow. The utility of “inconsistent” relevance maps to identify misclassified cases requires further investigation.

Editors' Note: Acute Hypokinetic-Rigid Syndrome After SARS-CoV-2 Infection.

In their case report, Dr. Méndez-Guerrero and colleagues add to the growing literature suggesting the neuroinvasive potential and neurologic sequelae of infection with the novel human coronavirus, SARS-CoV-2. Supported by dopamine transporter-SPECT imaging and negative testing for other known precipitants of Parkinsonism, this case exemplifies a rapidly improving postinfectious hypokinetic-rigid syndrome with associated generalized myoclonus and opsoclonus in a critically ill patient with coronavirus disease 2019 (COVID-19). The authors go on to imply that their case is reminiscent of the infamous encephalitis lethargica described by Constantin von Economo in 1917. Dr. Joseph Berger, neurovirologist and authority on von Economo's encephalitis, contests the relationship between SARS-CoV-2 and the clinical/radiologic observations made by the authors. Instead, Dr. Berger posits, the observations may be the consequence of hypoxic ischemic injury. In addition, the cases originally described by von Economo were observed years (not days) after an infectious illness. Dr. Shubhakaran recounts similar experiences with 2 patients who developed acute movement disorders after a viral prodrome; however, one was not tested for SARS-CoV-2 and the second tested negative by PCR. The authors maintain that their patient's oxygenation while intubated remained sufficient and would not have resulted in hypoxic ischemic injury. Furthermore, that the patient improved quickly and significantly would not be congruous with anoxic brain damage. The authors add credence to their argument by citing 2 related case reports of post-COVID-19 Parkinsonism that have been recently published. Nonetheless, we still need more clinical-pathological material to determine how neuroinvasive SARS-CoV-2 really is. In their case report, Dr. Méndez-Guerrero and colleagues add to the growing literature suggesting the neuroinvasive potential and neurologic sequelae of infection with the novel human coronavirus, SARS-CoV-2. Supported by dopamine transporter-SPECT imaging and negative testing for other known precipitants of Parkinsonism, this case exemplifies a rapidly improving postinfectious hypokinetic-rigid syndrome with associated generalized myoclonus and opsoclonus in a critically ill patient with coronavirus disease 2019 (COVID-19). The authors go on to imply that their case is reminiscent of the infamous encephalitis lethargica described by Constantin von Economo in 1917. Dr. Joseph Berger, neurovirologist and authority on von Economo's encephalitis, contests the relationship between SARS-CoV-2 and the clinical/radiologic observations made by the authors. Instead, Dr. Berger posits, the observations may be the consequence of hypoxic ischemic injury. In addition, the cases originally described by von Economo were observed years (not days) after an infectious illness. Dr. Shubhakaran recounts similar experiences with 2 patients who developed acute movement disorders after a viral prodrome; however, one was not tested for SARS-CoV-2 and the second tested negative by PCR. The authors maintain that their patient's oxygenation while intubated remained sufficient and would not have resulted in hypoxic ischemic injury. Furthermore, that the patient improved quickly and significantly would not be congruous with anoxic brain damage. The authors add credence to their argument by citing 2 related case reports of post-COVID-19 Parkinsonism that have been recently published. Nonetheless, we still need more clinical-pathological material to determine how neuroinvasive SARS-CoV-2 really is.

Using Artificial Neural Network to Discriminate Parkinson's Disease from Other Parkinsonisms by Focusing on Putamen of Dopamine Transporter SPECT Images.

Background: The challenge of differentiating, at an early stage, Parkinson’s disease from parkinsonism caused by other disorders remains unsolved. We proposed using an artificial neural network (ANN) to process images of dopamine transporter single-photon emission computed tomography (DAT-SPECT). Methods: Abnormal DAT-SPECT images of subjects with Parkinson’s disease and parkinsonism caused by other disorders were divided into training and test sets. Striatal regions of the images were segmented by using an active contour model and were used as the data to perform transfer learning on a pre-trained ANN to discriminate Parkinson’s disease from parkinsonism caused by other disorders. A support vector machine trained using parameters of semi-quantitative measurements including specific binding ratio and asymmetry index was used for comparison. Results: The predictive accuracy of the ANN classifier (86%) was higher than that of the support vector machine classifier (68%). The sensitivity and specificity of the ANN classifier in predicting Parkinson’s disease were 81.8% and 88.6%, respectively. Conclusions: The ANN classifier outperformed classical biomarkers in differentiating Parkinson’s disease from parkinsonism caused by other disorders. This classifier can be readily included into standalone computer software for clinical application.

Clinical Phenotypes in Corticobasal Syndrome with or without Amyloidosis Biomarkers.

Corticobasal syndrome (CBS) is a neuropathologically heterogeneous entity. The use of cerebrospinal fluid and amyloid biomarkers enables detection of underlying Alzheimer's disease (AD) pathology. We thus compared clinical, eye movement, and 18FDG-PET imaging characteristics in CBS in two groups of patients divided according to their amyloid biomarkers profile. Fourteen patients presenting with CBS and amyloidosis (CBS-A+) were compared with 16 CBS patients without amyloidosis (CBS-A-). The two groups showed similar motor abnormalities (parkinsonism, dystonia) and global cognitive functions. Unlike CBS-A+ patients who displayed more posterior cortical abnormalities, CBS-A- patients demonstrated more anterior cortical and brain stem dysfunctions on the basis of neuropsychological testing, study of saccade velocities and brain hypometabolism areas on 18FDG-PET. Interestingly, Dopamine Transporter SPECT imaging showed similar levels of dopaminergic degeneration in both groups. These findings confirm common and distinct brain abnormalities between the different neurodegenerative diseases that result in CBS. We demonstrate the importance of a multidisciplinary approach to improve diagnosis in vivo in particular on oculomotor examination.

Revision of Diagnosis in Early Parkinsonism with Abnormal Dopamine Transporter Imaging.

In patients with early parkinsonism, misdiagnosis may occur in >30% of cases. This can have detrimental consequences clinically and in clinical trials. Dopamine transporter (DAT) SPECT imaging can help improve diagnostic accuracy. To describe characteristics of individuals initially diagnosed with idiopathic Parkinson's disease (iPD) and with abnormal DAT SPECT imaging who had a change in diagnosis on follow-up. Data were obtained from the biomarker study Parkinson's Progression Markers Initiative (PPMI). PPMI is a multicenter, observational study that enrolled 423 individuals with a diagnosis of iPD of ≤2 years duration and with abnormal DAT SPECT imaging. Participants were assessed at least annually, and diagnosis was documented by the site neurologist. Characteristics of those that had a change in diagnosis were compared to those with stable diagnosis. 390 subjects were included. Eight (2%) had a change in diagnosis. The diagnosis was changed to multiple system atrophy in 5 cases, dementia with Lewy bodies in 2, and corticobasal degeneration in 1. Revision of diagnosis occurred 2-5.2 years from enrollment. Mean motor score was higher (26.9 vs 20.6; p = 0.01), DAT binding lower (1.056 vs 1.406; p = 0.01), genetic risk score lower (-0.016 vs -0.022; p = 0.0470), and olfaction score higher (28.75 vs 22.05; p = 0.03) in those whose diagnosis changed compared to those who did not. Diagnosis remained stable in most individuals with early parkinsonism diagnosed with iPD and with abnormal DAT imaging. A small number had a revision in diagnosis. Clinical and biomarker abnormalities were greater at baseline in those whose diagnosis changed.

Quantifying the Severity of Parkinson Disease by Use of Dopaminergic Neuroimaging.

OBJECTIVE. Parkinson disease is characterized by dopaminergic neuron loss in the substantia nigra pars compacta resulting in presynaptic nigrostriatal dopamine dysfunction. The purpose of this study was to search for an optimal image biomarker to quantify the severity of Parkinson disease by comparing neuromelanin MRI and dopamine transporter SPECT. SUBJECTS AND METHODS. Forty patients with Parkinson disease (Hoehn and Yahr [HY] stage 1, four patients; stage 2, 18 patients; stage 3, eight patients; stage 4, six patients; stage 5, four patients) who underwent neuromelanin MRI and dopamine transporter SPECT were included. The signal-to-noise ratio (SNR) in the substantia nigra pars compacta on neuromelanin MR images and the striatal specific binding ratio (SBR) on dopamine transporter SPECT images were calculated on the basis of the value of each background region. The Mann-Whitney U test was used to test the significance of difference between the early-stage group (HY stages 1 and 2) and the advanced-stage group (HY stages 3-5) for each SNR and SBR. ROC analysis was used to compare intergroup discriminating performance. The correlation of each SNR and SBR with clinical rating scale was assessed. RESULTS. Both SNR and SBR were significantly greater in the early-stage group than in the advanced-stage group (p < 0.05). The ROC AUCs for differentiating the two groups were 0.73 for SNR and 0.89 for SBR. The coefficients of correlation were -0.47 for SNR versus HY stage and -0.67 for SBR versus HY stage. CONCLUSION. Dopaminergic neuroimaging, particularly dopamine transporter SPECT, is a potentially useful imaging biomarker of the severity of Parkinson disease.

SUCCESSFUL USE OF ELECTROCONVULSIVE THERAPY FOR THE TREATMENT OF NEUROPSYCHIATRIC MANIFESTATIONS OF DEMENTIA WITH LEWY BODIES

Introduction Dementia with Lewy bodies (DLB) is one of the most common neurodegenerative disorders. DLB is characterized by progressive cognitive decline, executive dysfunction, visual hallucinations, fluctuating cognition, and Parkinsonism. Up to 65% of patients with Lewy Body Dementia have depression. Psychiatrists frequently treat individuals with DLB given prominent neuropsychiatric manifestations, including depression, hallucinations, delusions, agitation, and fluctuating cognition. Individuals with DLB require a comprehensive but specific treatment approach given sensitivity to both antipsychotic medications and anticholinergic side effects of other medications. Electroconvulsive therapy (ECT) is often omitted from the treatment model for DLB because of limited evidence. We highlight the use of electroconvulsive therapy (ECT) in a case of DLB. Methods We provide a case report and literature review on the use of ECT for the treatment of DLB. A 67-year-old male veteran with depression, 10-year history of REM sleep behavior disorder, bradykinesia, three-year history of cognitive impairment, and visual hallucinations was admitted for depressed mood and disturbing visual hallucinations featuring a saw blade swinging around his head and somatic delusion of a water hose traversing his body. At night he moved to avoid being hit by the blade. His wife reported word-finding difficulty, memory problems, and having to manage their finances. Four years prior to presentation, he stopped working as a pastor due to inability to write sermons. On admission, his MOCA was 19/30 and QIDS was 22. Medication trials including paroxetine, sertraline, escitalopram, vilazodone, bupropion, mirtazapine, venlafaxine, quetiapine, aripiprazole, alprazolam, buspirone, and lorazepam failed to address his depression and hallucinations. Results Brain MRI was unremarkable, with mild microvascular ischemic changes in periventricular white matter. Iodine-123 dopamine transporter SPECT (DAT-scan) imaging showed abnormal uptake consistent with a Parkinsonian syndrome (supporting the diagnosis of DLB). Considering past medication failures, patient consented for an acute course of ECT. He received eight right unilateral (RUL) ultra-brief pulse treatments utilizing Mecta Spectrum over the course of three weeks without any major side effects. For muscle relaxation he received succinylcholine; methohexital and remifentanil were given for anesthesia. Over his acute course of treatment, charge was progressively increased from six, to eight, to ten times the seizure threshold. At the end of his acute course of eight ECT treatments, his MOCA improved from 19/30 to 23/30 and QIDS improved from 22 to 12. Following the course of ECT, his visual hallucinations disappeared, and he was more interactive, engaged, and less depressed. The patient's improvement is congruent with other case reports in the literature showing clinical improvement following ECT for symptoms related to DLB. A table with a literature review describing the use of ECT for DLB will be presented. Conclusions DLB presents frequently to psychiatrists secondary to prominent psychiatric manifestations of the illness such as mood and behavioral disturbances. The treatment of psychiatric symptoms in DLB is often challenging due to the sensitivity of antidopaminergic medications on motor symptoms. ECT is a feasible alternative to treat neuropsychiatric manifestations of DLB; however, infrequently considered due to fear of complications and stigma. Modifications to the treatment such us holding dopamine agonists the morning of ECT to avoid delirium, decreasing the frequency of ECT to twice per week to minimize cognitive effects, and close monitoring of the patient's cognitive function are measures that can be implemented to optimize ECT in this population. No double-blinded randomized control trials exist in this area; comparing standard treatment to ECT would help further delineate the role of ECT in treating patients with DLB. This research was funded by None.

Basic clinical features do not predict dopamine transporter binding in idiopathic REM behavior disorder

REM sleep behavior disorder (RBD) is strongly associated with development of Parkinson’s Disease and other α-synuclein-related disorders. Dopamine transporter (DAT) binding deficit predicts conversion to α-synuclein-related disorders in individuals with RBD. In turn, identifying which individuals with RBD have the highest likelihood of having abnormal DAT binding would be useful. The objective of this analysis was to examine if there are basic clinical predictors of DAT deficit in RBD. Participants referred for inclusion in the RBD cohort of the Parkinson Progression Markers Initiative were included. Assessments at the screening visit including DAT SPECT imaging, physical examination, cognitive function screen, and questionnaire-based non-motor assessment. The group with DAT binding deficit (n = 49) was compared to those without (n = 26). There were no significant differences in demographic or clinical features between the two groups. When recruiting RBD cohorts enriched for high risk of neurodegenerative disorders, our data support the need for objective biomarker assessments.

The applicability of 123I-FP-CIT SPECT dopamine transporter imaging in clinical practice

The 123I-FP-CIT dopamine transporter SPECT imaging is a sensitive method to assess functional dopaminergic neuron terminals in the striatum. The method has also been available in Hungary for years. There are two main indications: (i) to help differentiate essential tremor from clinically uncertain Parkinsonism, including patients with early symptoms and (ii) to help differentiate dementia with Lewy bodies from Alzheimer's disease. The aim of this paper is to review 123I-FP-CIT SPECT imaging based on international data/guidelines and our own experiences, thereby assisting nuclear medicine practitioners and neurologists.

Improvement in the measurement error of the specific binding ratio in dopamine transporter SPECT imaging due to exclusion of the cerebrospinal fluid fraction using the threshold of voxel RI count.

In Japan, the Southampton method for dopamine transporter (DAT) SPECT is widely used to quantitatively evaluate striatal radioactivity. The specific binding ratio (SBR) is the ratio of specific to non-specific binding observed after placing pentagonal striatal voxels of interest (VOIs) as references. Although the method can reduce the partial volume effect, the SBR may fluctuate due to the presence of low-count areas of cerebrospinal fluid (CSF), caused by brain atrophy, in the striatal VOIs. We examined the effect of the exclusion of low-count VOIs on SBR measurement. We retrospectively reviewed DAT imaging of 36 patients with parkinsonian syndromes performed after injection of 123I-FP-CIT. SPECT data were reconstructed using three conditions. We defined the CSF area in each SPECT image after segmenting the brain tissues. A merged image of gray and white matter images was constructed from each patient's magnetic resonance imaging (MRI) to create an idealized brain image that excluded the CSF fraction (MRI-mask method). We calculated the SBR and asymmetric index (AI) in the MRI-mask method for each reconstruction condition. We then calculated the mean and standard deviation (SD) of voxel RI counts in the reference VOI without the striatal VOIs in each image, and determined the SBR by excluding the low-count pixels (threshold method) using five thresholds: mean-0.0SD, mean-0.5SD, mean-1.0SD, mean-1.5SD, and mean-2.0SD. We also calculated the AIs from the SBRs measured using the threshold method. We examined the correlation among the SBRs of the threshold method, between the uncorrected SBRs and the SBRs of the MRI-mask method, and between the uncorrected AIs and the AIs of the MRI-mask method. The intraclass correlation coefficient indicated an extremely high correlation among the SBRs and among the AIs of the MRI-mask and threshold methods at thresholds between mean-2.0D and mean-1.0SD, regardless of the reconstruction correction. The differences among the SBRs and the AIs of the two methods were smallest at thresholds between man-2.0SD and mean-1.0SD. The SBR calculated using the threshold method was highly correlated with the MRI-SBR. These results suggest that the CSF correction of the threshold method is effective for the calculation of idealized SBR and AI values.

123I-FP-CIT SPECT Accurately Distinguishes Parkinsonian From Cerebellar Variant of Multiple System Atrophy.

Dopamine transporter SPECT imaging is a valuable tool to estimate the integrity of presynaptic dopaminergic pathways in degenerative parkinsonisms. Evidence about SPECT differential pattern between parkinsonian and cerebellar forms of multiple system atrophy (MSA-P and MSA-C) is lacking. We aimed at assessing whether MSA-P and MSA-C variants have a distinct semiquantitative I-FP-CIT SPECT pattern. We studied a unicentric 13-year (2003-2016) retrospective cohort of subjects with possible or probable MSA and scanned with the same acquisition and reconstruction SPECT protocol. Age-dependent semiquantitative reference limits for striatal volumes of interest, asymmetry indices, and caudate/putamen ratio were previously established with a percentile approach on a cohort of subjects with nondegenerative conditions and normal visual scan. Thirty-four subjects with clinical MSA (28 MSA-P and 6 MSA-C) were identified (mean age, 68.2 ± 10.1 years; male/female ratio 1.00; disease duration, 2.5 ± 2.2 years; Movement Disorders Society Unified Parkinson's Disease Rating Scale III score, 33.8 ± 12.4). The MSA-P subjects exhibited lower uptake values for all volumes of interest, for example, striatal uptake on the more affected side (1.10 ± 0.51) compared with MSA-C (2.30 ± 0.41, P = 0.0005), as well as significantly higher asymmetry indices % (24.7 ± 24.8 vs 6.3 ± 4.5, P = 0.028) and caudate/putamen ratio (2.26 ± 1.23 vs 1.13 ± 0.17, P = 0.00148). The MSA-P and MSA-C subjects exhibited significantly distinct semiquantitative SPECT pattern with severe uptake impairment and high asymmetry for MSA-P and borderline uptake values for MSA-C. Clinical distinction of these 2 phenotypical entities is necessary in order to evaluate SPECT potential to discriminate between degenerative parkinsonisms.

Evaluation of the Reconstruction Parameters of Brain Dopamine Transporter SPECT images Obtained by a Fan Beam Collimator: A Comparison with Parallel-hole Collimators.

Objective(s):The purpose of this study was to examine the optimal reconstruction parameters for brain dopamine transporter SPECT images obtained with a fan beam collimator and compare the results with those obtained by using parallel-hole collimators. Methods:Data acquisition was performed using two SPECT/CT devices, namely a Symbia T6 and an Infinia Hawkeye 4 (device A and B) equipped with fan-beam (camera A-1 and B-1), low- and medium-energy general-purpose (camera A-2 and B-2), and low-energy high-resolution (camera A-3 and B-3) collimators. The SPECT images were reconstructed using filtered back projection (FBP) with Chang’s attenuation correction. However, the scatter correction was not performed. A pool phantom and a three-dimensional (3D) brain phantom were filled with 123I solution to examine the reconstruction parameters. The optimal attenuation coefficient was based on the visual assessment of the profile curve, coefficient of variation (CV) [%], and summed difference from the reference activity of the pool phantom. The optimal Butterworth filter for the 3D-brain phantom was also determined based on a visual assessment. The anthropomorphic striatal phantom was filled with 123I solution at striatum-to-background radioactivity ratios of 8, 6, 4, and 3. The specific binding ratio (SBR) of the striatum (calculated by the CT method) was used to compare the results with those of the parallel-hole collimators.Results:The optimal attenuation coefficients were 0.09, 0.11, 0.05, 0.05, 0.11, and, 0.10 cm-1 for cameras A-1, A-2, A-3, B-1, B-2, and B-3, respectively. The cutoff frequencies of the Butterworth filter were 0.32, 0.40, and 0.36 cycles/cm for camera A, and 0.46, 0.44, and 0.44 cycles/cm for camera B, respectively. The recovery rates of the SBRmean with camera A were 51.2%, 49.4%, and 45.6%, respectively. The difference was not statistically significant. The recovery rates of the SBR with camera B were 59.2%, 50.7%, and 50.8%, respectively. Camera B-1 showed significantly high SBR values.Conclusion:As the findings indicated, the optimal reconstruction parameters differed according to the devices and collimators. The fan beam collimator was found to provide promising results with each device.

Dopamine transporter imaging does not predict the number of nigral neurons in Parkinson disease.

To examine possible associations between in vivo brain dopamine transporter SPECT imaging and substantia nigra pars compacta (SNc) neuronal survival in Parkinson disease (PD). Nigral neuron numbers were calculated for 18 patients (11 patients with neuropathologically confirmed PD) who had been examined with dopamine transporter (DAT) SPECT before death. Correlation analyses between SNc tyrosine hydroxylase (TH)-positive and neuromelanin-containing neuron counts and DAT striatal specific binding ratios (SBRs) were performed with semiquantitative region of interest-based and voxel-based analyses. Mean putamen SBR did not correlate with the number of substantia nigra TH-positive (r = -0.11, p = 0.66) or neuromelanin-containing (r = -0.07, p = 0.78) neurons. Correlations remained clearly nonsignificant when the time interval between SPECT and death was used as a covariate, when the voxel-based analysis was used, and when only patients with PD were included. This cohort study demonstrates that postmortem SNc neuron counts are not associated with striatal DAT binding in PD. These results fit with the theory that there is no correlation between the number of substantia nigra neurons and striatal dopamine after a certain level of damage has occurred. Striatal DAT binding in PD may reflect axonal dysfunction or DAT expression rather than the number of viable neurons.

Improved prediction of outcome in Parkinson's disease using radiomics analysis of longitudinal DAT SPECT images.

No disease modifying therapies for Parkinson's disease (PD) have been found effective to date. To properly power clinical trials for discovery of such therapies, the ability to predict outcome in PD is critical, and there is a significant need for discovery of prognostic biomarkers of PD. Dopamine transporter (DAT) SPECT imaging is widely used for diagnostic purposes in PD. In the present work, we aimed to evaluate whether longitudinal DAT SPECT imaging can significantly improve prediction of outcome in PD patients. In particular, we investigated whether radiomics analysis of DAT SPECT images, in addition to use of conventional non-imaging and imaging measures, could be used to predict motor severity at year 4 in PD subjects. We selected 64 PD subjects (38 male, 26 female; age at baseline (year 0): 61.9 ± 7.3, range [46,78]) from the Parkinson's Progressive Marker Initiative (PPMI) database. Inclusion criteria included (i) having had at least 2 SPECT scans at years 0 and 1 acquired on a similar scanner, (ii) having undergone a high-resolution 3 T MRI scan, and (iii) having motor assessment (MDS-UPDRS-III) available in year 4 used as outcome measure. Image analysis included automatic region-of-interest (ROI) extraction on MRI images, registration of SPECT images onto the corresponding MRI images, and extraction of radiomic features. Non-imaging predictors included demographics, disease duration as well as motor and non-motor clinical measures in years 0 and 1. The image predictors included 92 radiomic features extracted from the caudate, putamen, and ventral striatum of DAT SPECT images at years 0 and 1 to quantify heterogeneity and texture in uptake. Random forest (RF) analysis with 5000 trees was used to combine both non-imaging and imaging variables to predict motor outcome (UPDRS-III: 27.3 ± 14.7, range [3,77]). The RF prediction was evaluated using leave-one-out cross-validation. Our results demonstrated that addition of radiomic features to conventional measures significantly improved (p < 0.001) prediction of outcome, reducing the absolute error of predicting MDS-UPDRS-III from 9.00 ± 0.88 to 4.12 ± 0.43. This shows that radiomics analysis of DAT SPECT images has a significant potential towards development of effective prognostic biomarkers in PD.

Application of texture analysis to DAT SPECT imaging: Relationship to clinical assessments.

Dopamine transporter (DAT) SPECT imaging is increasingly utilized for diagnostic purposes in suspected Parkinsonian syndromes. We performed a cross-sectional study to investigate whether assessment of texture in DAT SPECT radiotracer uptake enables enhanced correlations with severity of motor and cognitive symptoms in Parkinson's disease (PD), with the long-term goal of enabling clinical utility of DAT SPECT imaging, beyond standard diagnostic tasks, to tracking of progression in PD. Quantitative analysis in routine DAT SPECT imaging, if performed at all, has been restricted to assessment of mean regional uptake. We applied a framework wherein textural features were extracted from the images. Notably, the framework did not require registration to a common template, and worked in the subject-native space. Image analysis included registration of SPECT images onto corresponding MRI images, automatic region-of-interest (ROI) extraction on the MRI images, followed by computation of Haralick texture features. We analyzed 141 subjects from the Parkinson's Progressive Marker Initiative (PPMI) database, including 85 PD and 56 healthy controls (HC) (baseline scans with accompanying 3 T MRI images). We performed univariate and multivariate regression analyses between the quantitative metrics and different clinical measures, namely (i) the UPDRS (part III - motor) score, disease duration as measured from (ii) time of diagnosis (DD-diag.) and (iii) time of appearance of symptoms (DD-sympt.), as well as (iv) the Montreal Cognitive Assessment (MoCA) score. For conventional mean uptake analysis in the putamen, we showed significant correlations with clinical measures only when both HC and PD were included (Pearson correlation r = − 0.74, p-value < 0.001). However, this was not significant when applied to PD subjects only (r = − 0.19, p-value = 0.084), and no such correlations were observed in the caudate. By contrast, for the PD subjects, significant correlations were observed in the caudate when including texture metrics, with (i) UPDRS (p-values < 0.01), (ii) DD-diag. (p-values < 0.001), (iii) DD-sympt (p-values < 0.05), and (iv) MoCA (p-values < 0.01), while no correlations were observed for conventional analysis (p-values = 0.94, 0.34, 0.88 and 0.96, respectively). Our results demonstrated the ability to capture valuable information using advanced texture metrics from striatal DAT SPECT, enabling significant correlations of striatal DAT binding with clinical, motor and cognitive outcomes, and suggesting that textural features hold potential as biomarkers of PD severity and progression.