Metabolic network alterations as a supportive biomarker in dementia with Lewy bodies with preserved dopamine transmission.

PURPOSE: Metabolic network analysis of FDG-PET utilizes an index of inter-regional correlation of resting state glucose metabolism and has been proven to provide complementary information regarding the disease process in parkinsonian syndromes. The goals of this study were (i) to evaluate pattern similarities of glucose metabolism and network connectivity in dementia with Lewy bodies (DLB) subjects with subthreshold dopaminergic loss compared to advanced disease stages and to (ii) investigate metabolic network alterations of FDG-PET for discrimination of patients with early DLB from other neurodegenerative disorders (Alzheimer's disease, Parkinson's disease, multiple system atrophy) at individual patient level via principal component analysis (PCA). METHODS: FDG-PETs of subjects with probable or possible DLB (n = 22) without significant dopamine deficiency (z-score < 2 in putamen binding loss on DaT-SPECT compared to healthy controls (HC)) were scaled by global-mean, prior to volume-of-interest-based analyses of relative glucose metabolism. Single region metabolic changes and network connectivity changes were compared against HC (n = 23) and against DLB subjects with significant dopamine deficiency (n = 86). PCA was applied to test discrimination of patients with DLB from disease controls (n = 101) at individual patient level. RESULTS: Similar patterns of hypo- (parietal- and occipital cortex) and hypermetabolism (basal ganglia, limbic system, motor cortices) were observed in DLB patients with and without significant dopamine deficiency when compared to HC. Metabolic connectivity alterations correlated between DLB patients with and without significant dopamine deficiency (R2 = 0.597, p < 0.01). A PCA trained by DLB patients with dopamine deficiency and HC discriminated DLB patients without significant dopaminergic loss from other neurodegenerative parkinsonian disorders at individual patient level (area-under-the-curve (AUC): 0.912). CONCLUSION: Disease-specific patterns of altered glucose metabolism and altered metabolic networks are present in DLB subjects without significant dopaminergic loss. Metabolic network alterations in FDG-PET can act as a supporting biomarker in the subgroup of DLB patients without significant dopaminergic loss at symptoms onset.

CYP3A4 inhibitors may influence the quantification of [123I]I-FP-CIT SPECT scans.

PURPOSE: [123I]I-FP-CIT SPECT is an imaging tool to support the diagnosis of parkinsonian syndromes characterized by nigrostriatal dopaminergic degeneration. After intravenous injection, [123I]I-FP-CIT is metabolized for a small part by the enzyme CYP3A4, leading to the formation of [123I]I-nor-ß-CIT. [123I]I-nor-ß-CIT passes the blood-brain barrier and has a very high affinity for the serotonin transporter (SERT). The SERT is expressed in the striatum and cortical areas. So, at least theoretical, the use of frequently used CYP3A4 inhibitors (like amiodarone) may influence the specific to non-specific striatal [123I]I-FP-CIT ratio. Here we tested this novel hypothesis. METHODS: Using a retrospective design, we determined the specific to non-specific striatal [123I]I-FP-CIT ratio (using BRASS software) in 6 subjects that were using an CYP3A4 inhibitor and 18 matched controls. Only subjects were included with a normal rated [123I]I-FP-CIT SPECT scan, and all participants were scanned on the same brain-dedicated SPECT system. RESULTS: The specific to non-specific (assessed in the occipital cortex) striatal [123I]I-FP-CIT binding ratio was significantly higher in CYP3A4 users than in the control group (3.52 ± 0.33 vs. 2.90 ± 0.78, p < 0.001). CONCLUSION: Our preliminary data suggest that the use of CYP3A4 inhibitors may influence striatal [123I]I-FP-CIT binding ratios. This information, when reproduced in larger studies, may be relevant for studies in which quantification of [123I]I-FP-CIT SPECT imaging is used for diagnostic or research purposes.

Abnormal dopamine transporter imaging in pure autonomic failure: a potential biomarker of central nervous system involvement.

BACKGROUND AND PURPOSE: Pure autonomic failure (PAF) is a rare progressive neurodegenerative disease characterized by neurogenic orthostatic hypotension at presentation, without other neurological abnormalities. Some patients may develop other central neurological features indicative of multiple system atrophy or a Lewy body disorder. There are currently no biomarkers to assess possible central nervous system involvement in probable PAF at an early stage. A possibility is to evaluate the nigrostriatal dopaminergic degeneration by imaging of dopamine transporter with DaTscan brain imaging. The objective was to evaluate subclinical central nervous system involvement using DaTscan in PAF. METHODS: We retreospectively reviewed pure autonomic failure patients who were evaluated at the Autonomic Unit between January 2015 and August 2021 and underwent comprehensive autonomic assessment, neurological examination, brain magnetic resonance imaging and DaTscan imaging. DaTscan imaging was performed if patients presented with atypical features which did not meet the criteria for Parkinson's disease or multiple system atrophy or other atypical parkinsonism. RESULTS: In this cohort, the median age was 49.5 years at disease onset, 57.5 years at presentation, and the median disease duration was 7.5 years. Five of 10 patients had an abnormal DaTscan without neurological features meeting the criteria of an alternative diagnosis. Patients with abnormal DaTscan were predominantly males, had shorter disease duration and had more severe genitourinary symptoms. DISCUSSION: Degeneration of nigrostriatal dopaminergic neurons measured using DaTscan imaging can present in patients with PAF without concurrent signs indicating progression to widespread α-synucleinopathy. It is advocated that DaTscan imaging should be considered as part of the workup of patients with emerging autonomic failure who are considered to have PAF.

An improved method for diagnosis of Parkinson's disease using deep learning models enhanced with metaheuristic algorithm.

Parkinson's disease (PD) is challenging for clinicians to accurately diagnose in the early stages. Quantitative measures of brain health can be obtained safely and non-invasively using medical imaging techniques like magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT). For accurate diagnosis of PD, powerful machine learning and deep learning models as well as the effectiveness of medical imaging tools for assessing neurological health are required. This study proposes four deep learning models with a hybrid model for the early detection of PD. For the simulation study, two standard datasets are chosen. Further to improve the performance of the models, grey wolf optimization (GWO) is used to automatically fine-tune the hyperparameters of the models. The GWO-VGG16, GWO-DenseNet, GWO-DenseNet + LSTM, GWO-InceptionV3 and GWO-VGG16 + InceptionV3 are applied to the T1,T2-weighted and SPECT DaTscan datasets. All the models performed well and obtained near or above 99% accuracy. The highest accuracy of 99.94% and AUC of 99.99% is achieved by the hybrid model (GWO-VGG16 + InceptionV3) for T1,T2-weighted dataset and 100% accuracy and 99.92% AUC is recorded for GWO-VGG16 + InceptionV3 models using SPECT DaTscan dataset.

A systematic review of the potential effects of medications and drugs of abuse on dopamine transporter imaging using [123I]I-FP-CIT SPECT in routine practice.

PURPOSE: In routine practice, dopamine transporter (DAT) imaging is frequently used as a diagnostic tool to support the diagnosis of Parkinson's disease or dementia with Lewy bodies. In 2008, we published a review on which medications and drugs of abuse may influence striatal [123I]I-FP-CIT binding and consequently may influence the visual read of an [123I]I-FP-CIT SPECT scan. We made recommendations on which drugs should be withdrawn before performing DAT imaging in routine practice. Here, we provide an update of the original work based on published research since 2008. METHODS: We performed a systematic review of literature without language restriction from January 2008 until November 2022 to evaluate the possible effects of medications and drugs of abuse, including the use of tobacco and alcohol, on striatal DAT binding in humans. RESULTS: The systematic literature search identified 838 unique publications, of which 44 clinical studies were selected. Using this approach, we found additional evidence to support our original recommendations as well as some new findings on potential effect of other medications on striatal DAT binding. Consequently, we updated the list of medications and drugs of abuse that may influence the visual read of [123I]I-FP-CIT SPECT scans in routine clinical practice. CONCLUSION: We expect that a timely withdrawal of these medications and drugs of abuse before DAT imaging may reduce the incidence of false-positive reporting. Nevertheless, the decision to withdraw any medication must be made by the specialist in charge of the patient's care and considering the pros and cons of doing so.

The diagnostic performance of functional dopaminergic scintigraphic imaging in the diagnosis of dementia with Lewy bodies: an updated systematic review.

INTRODUCTION: Dopaminergic scintigraphic imaging is a cornerstone to support the diagnosis in dementia with Lewy bodies. To clarify the current state of knowledge on this imaging modality and its impact on clinical diagnosis, we performed an updated systematic review of the literature. METHODS: This systematic review was carried out according to PRISMA guidelines. A comprehensive computer literature search of PubMed/MEDLINE, EMBASE, and Cochrane Library databases for studies published through June 2022 was performed using the following search algorithm: (a) "Lewy body" [TI] OR "Lewy bodies" [TI] and (b) ("DaTscan" OR "ioflupane" OR "123ip" OR "123?ip" OR "123 ip" OR "123i-FP-CIT" OR "FPCIT" OR "FP-CIT" OR "beta?CIT" OR "beta CIT" OR "CIT?SPECT" OR "CIT SPECT" OR "Dat?scan*" OR "dat scan*" OR "dat?spect*" OR "SPECT"). Risk of bias and applicability concerns of the studies were evaluated using the QUADAS-2 tool. RESULTS: We performed a qualitative analysis of 59 studies. Of the 59 studies, 19 (32%) addressed the diagnostic performance of dopamine transporter imaging, 15 (25%) assessed the identification of dementia with Lewy bodies in the spectrum of Lewy body disease and 18 (31%) investigated the role of functional dopaminergic imaging in distinguishing dementia with Lewy bodies from other dementias. Dopamine transporter loss was correlated with clinical outcomes in 19 studies (32%) and with other functional imaging modalities in 15 studies (25%). Heterogeneous technical aspects were found among the studies through the use of various radioligands, the more prevalent being the [123I]N­ω­fluoropropyl­2ß­carbomethoxy­3ß­(4­iodophenyl) nortropane (123I-FP-CIT) in 54 studies (91.5%). Image analysis used visual analysis (9 studies, 15%), semi-quantitative analysis (29 studies, 49%), or a combination of both (16 studies, 27%). CONCLUSION: Our systematic review confirms the major role of dopaminergic scintigraphic imaging in the assessment of dementia with Lewy bodies. Early diagnosis could be facilitated by identifying the prodromes of dementia with Lewy bodies using dopaminergic scintigraphic imaging coupled with emphasis on clinical neuropsychiatric symptoms. Most published studies use a semi-quantitative analytical assessment of tracer uptake, while there are no studies using quantitative analytical methods to measure dopamine transporter loss. The superiority of a purely quantitative approach to assess dopaminergic transmission more accurately needs to be further clarified.

Pilot Study for Correlation of Heart Rate Variability and Dopamine Transporter Brain Imaging in Patients with Parkinsonian Syndrome.

BACKGROUND: Parkinsonian syndrome (PS) is a broad category of neurodegenerative movement disorders that includes Parkinson disease, multiple system atrophy (MSA), progressive supranuclear palsy, and corticobasal degeneration. Parkinson disease (PD) is the second most common neurodegenerative disorder with loss of dopaminergic neurons of the substantia nigra and, thus, dysfunction of the nigrostriatal pathway. In addition to the motor symptoms of bradykinesia, rigidity, tremors, and postural instability, nonmotor symptoms such as autonomic dysregulation (AutD) can also occur. Heart rate variability (HRV) has been used as a measure of AutD and has shown to be prognostic in diseases such as diabetes mellitus and cirrhosis, as well as PD. I-123 ioflupane, a gamma ray-emitting radiopharmaceutical used in single-photon emission computed tomography (SPECT), is used to measure the loss of dopaminergic neurons in PD. Through the combination of SPECT and HRV, we tested the hypothesis that asymmetrically worse left-sided neuronal loss would cause greater AutD. METHODS: 51 patients were enrolled on the day of their standard of care I-123 ioflupane scan for the work-up of possible Parkinsonian syndrome. Demographic information, medical and medication history, and ECG data were collected. HRV metrics were extracted from the ECG data. I-123 ioflupane scans were interpreted by a board-certified nuclear radiologist and quantified by automated software to generate striatal binding ratios (SBRs). Statistical analyses were performed to find correlations between the HRV and SPECT parameters. RESULTS: 32 patients were excluded from the final analysis because of normal scans, prior strokes, cardiac disorders and procedures, or cancer. Abnormal I-123 ioflupane scans were clustered using T-SNE, and one-way ANOVA was performed to compare HRV and SBR parameters. The analysis was repeated after the exclusion of patients taking angiotensin-converting enzyme inhibitors, given the known mechanism on autonomic function. Subsequent analysis showed a significant difference between the high-frequency domains of heart rate variability, asymmetry of the caudate SBR, and putamen-to-caudate SBR. CONCLUSION: Our results support the hypothesis that more imbalanced (specifically worse left-sided) neuronal loss results in greater AutD.

Dopamine denervation in the functional territories of the striatum: a new MR and atlas-based 123I-FP-CIT SPECT quantification method.

Current quantification methods of 123I-FP-CIT SPECT rely on anatomical parcellation of the striatum. We propose here to implement a new method based on MRI segmentation and functional atlas of the basal ganglia (MR-ATLAS) that could provide a reliable quantification within the sensorimotor, associative, and limbic territories of the striatum. Patients with Parkinson's disease (PD), idiopathic rapid eye movement sleep behavioral disorder (iRBD), and healthy controls underwent 123I-FP-CIT SPECT, MRI, motor, and cognitive assessments. SPECT data were corrected for partial volume effects and registered to a functional atlas of the striatum to allow quantification in every functional region of the striatum (nucleus accumbens, limbic, associative, and sensorimotor parts of the striatum). The MR-ATLAS quantification method is proved to be reliable in every territory of the striatum. In addition, good correlations were found between cognitive dysexecutive tests and the binding within the functional (limbic) territories of the striatum using the MR-ATLAS method, slightly better than correlations found using the anatomical quantification method. This new MR-ATLAS method provides a robust and useful tool for studying the dopaminergic system in PD, particularly with respect to cognitive functions. It may also be relevant to further unravel the relationship between dopaminergic denervation and cognitive or behavioral symptoms.

Positive DAT-SCAN in SPG7: a case report mimicking possible MSA-C.

BACKGROUND: Spastic Paraplegia type 7 (SPG7) is one of the most common autosomal recessive Hereditary Spastic Paraplegias (HSP); Spastic Paraplegias (SPGs) can present as hereditary ataxias. However, ataxia is frequently the symptom of presentation of many other hereditary/sporadic disorders, such as Multiple system atrophy type C (MSA-C), an α-synuclein sporadic neurodegenerative disorder, in which cerebellar ataxia is one of the main clinical features. Dopamine Transporter imaging (DAT-SCAN), associated with clinical features, can be a helpful tool in order to distinguish MSA-C from other causes of ataxia. CASE-PRESENTATION: We present the case of a 70-year-old man with gait difficulties over a period of 3 years and frequent backward/lateral falls. He also reported urinary urge incontinence, but no symptoms that are compatible with orthostatic hypotension. On neurological examination he showed ataxic gait, spasticity in the left lower limb and trunk and limb ataxia, especially on the left side. Mild hypokinesia was found in all 4 limbs, especially in the left foot. MRI revealed atrophy of the cerebellar hemispheres and vermis. DAT-SCAN imaging revealed bilateral nigro-striatal degeneration, which was compatible with a diagnosis of possible MSA-C. Considering the atypical disease course (the patient walked without any support after 3 years), we carried out a genetic investigation for Ataxia, and a mutation in SPG7 was found. CONCLUSIONS: DAT-SCAN imaging, evaluated together with the clinical findings, can be useful for differentiating MSA from other possible causes of adult-onset Ataxia. Indeed, patients with MSA-C generally show a decreased uptake of dopamine transporters in DAT-SCAN imaging. Ours is the first case reported in the literature of a patient with SPG7 mutation with nigrostriatal degeneration and a clinical presentation of a possible MSA-C. Performing genetic investigations in patients with an atypical disease course is important to avoid MSA-mimicries. Identifying the correct diagnosis is important not only for prognostic reasons, but also for possible future genetic therapies.

Genetic Architecture and Molecular, Imaging and Prodromic Markers in Dementia with Lewy Bodies: State of the Art, Opportunities and Challenges.

Dementia with Lewy bodies (DLB) is one of the most common causes of dementia and belongs to the group of α-synucleinopathies. Due to its clinical overlap with other neurodegenerative disorders and its high clinical heterogeneity, the clinical differential diagnosis of DLB from other similar disorders is often difficult and it is frequently underdiagnosed. Moreover, its genetic etiology has been studied only recently due to the unavailability of large cohorts with a certain diagnosis and shows genetic heterogeneity with a rare contribution of pathogenic mutations and relatively common risk factors. The rapid increase in the reported cases of DLB highlights the need for an easy, efficient and accurate diagnosis of the disease in its initial stages in order to halt or delay the progression. The currently used diagnostic methods proposed by the International DLB consortium rely on a list of criteria that comprises both clinical observations and the use of biomarkers. Herein, we summarize the up-to-now reported knowledge on the genetic architecture of DLB and discuss the use of prodromal biomarkers as well as recent promising candidates from alternative body fluids and new imaging techniques.

Neuroimaging in Parkinson's Disease: necessity or exaggeration?

INTRODUCTION: Neuroimaging plays an increasingly important role in the diagnosis of parkinsonian syndromes. AIM OF THE STUDY: In this paper, the authors elaborate on the necessity of using magnetic resonance imaging (MRI) in Parkinson's Disease (PD) and its potential role in differential diagnosis versus other neurodegenerative parkinsonian syndromes such as dementia with Lewy bodies, multiple system atrophy, progressive supranuclear palsy and corticobasal syndrome. STATE OF THE ART: The currently known characteristic abnormalities are listed and tabulated, current recommendations are summarised and sample images are provided. As routine MRI scanning in PD remains controversial, the authors' aim is to show the pros and cons in clinical practice. Additionally, the rationale for functional imaging examination, including [123I]-FP-CIT SPECT (DaTSCAN) and [99mTc]- HMPAO-SPECT, [18F]-FDG-PET, [123I]-mIBG-SPECT is discussed. CLINICAL VIGNETTE: This paper is accompanied by two illustrative clinical cases in which neuroimaging studies played a key role in diagnosis and further management. CONCLUSIONS: Neuroimaging can be helpful in differentiating PD from both atypical and symptomatic parkinsonism. Nevertheless, extensive neurological assessment in a majority of PD cases is sufficient to make a diagnosis. A network of specialists in movement disorders should be established in order to enable better, faster and more precise diagnosis of parkinsonism.

High discriminatory ability of peripheral and CFSF biomarkers in Lewy body diseases.

Differential diagnosis between Parkinson's disease (PD) Parkinson's disease dementia (PDD), dementia with Lewy bodies (DLB), namely spectrum of Lewy bodies disorders (LBDs), may be challenging, and their common underlying pathophysiology is debated. Our aim was to examine relationships among neurodegenerative biomarkers [alpha-synuclein (α-Syn), Alzheimer's Disease (AD)-related (beta-amyloid Aß42, tau [total τΤ and phosphorylated τp-181]), dopaminergic imaging (DATSCAN-SPECT)] and spectrum of LBD. This is a cross-sectional prospective study in 30 PD, 18 PDD, 29 DLB patients and 30 healthy controls. We compared α-Syn in CSF, plasma and serum and CSF Aß42, τΤ and τp-181 across these groups. Correlations between such biomarkers and motor, cognitive/neuropsychiatric tests, and striatal asymmetry indexes were examined. CSF α-Syn was higher in DLB versus PD/PDD/controls, and lower in PD and PDD patients compared to controls (all p < 0.001). Serum α-Syn levels were higher in all patient groups compared to controls. After excluding those DLB patients with CSF AD profile, plasma and serum Syn levels were higher in the LBD group as a whole compared to controls. The combination of CSF α-Syn, serum α-Syn and Aß42 for comparison between PD and DLB [AUC = 0.96 (95% CI 0.90-1.00)] was significantly better when compared to serum α-Syn alone (p < 0.001). Correlation analyses of biomarkers with cognitive/neuropsychiatric scales revealed some associations, but no consistent, cohesive picture. Peripheral biomarkers such as serum α-Syn, and CSF α-Syn and Aß42 may contribute as potential biomarkers to separate LBDs from controls and to differentiate DLB from the other LBDs with high sensitivity and specificity among study groups.

Very early-onset of RBD with ADHD: a case report study.

We experienced a case of very early-onset REM sleep behavior disorder (RBD) with ADHD. This case showed typical RBD symptoms with REM sleep without atonia on polysomnography. Methylphenidate, which enhances the dopamine system, attenuated his ADHD symptoms but not RBD symptoms. We speculate that the dysfunction of the laterodorsal tegmental nucleus in the pontine was responsible for the symptoms of RBD and ADHD in this case. Very early-onset RBD is rare, and its profile is not well known. ADHD with dysfunction in the laterodorsal tegmental nucleus may form asubtype of ADHD that is commonly comorbid with very early-onset RBD.

Should non-movement specialists refer patients for SPECT-DaTSCAN?

BACKGROUND: SPECT with radioligand DaTSCAN (SPECT-DaTSCAN) is a sensitive tool used for assessing the functional integrity of the presynaptic part of the nigrostriatal dopaminergic system. The procedure is useful whenever there is a need to distinguish between neurodegenerative parkinsonism and other parkinsonian syndromes in subjects with equivocal signs and symptoms. It can be assumed that the neurologist's decision to perform SPECT-DaTSCAN depends on his or her experience and skill in the diagnosis of parkinsonian and tremor syndromes. AIMS: To assess the accuracy of referrals to SPECT-DATSCAN made by non-movement disorders specialists. MATERIAL AND METHODS: Sixty seven patients referred for SPECT-DaTSCAN by a general neurologist were studied. In all subjects, a movement disorder specialist performed the neurological examination, collected medical history, and analysed previous treatments and the results of diagnostic tests. RESULTS: Evaluation carried out by a movement disorder specialist did not confirm an indication for SPECT-DaTSCAN in 31 patients (46.3%). General neurologists needed support for clinical diagnosis with SPECT-DaTSCAN most frequently in subjects with parkinsonism even though they were presenting a full-blown disease manifestation and even though the patients met the diagnostic criteria for Parkinson's disease or one of the atypical parkinsonian syndromes. CONCLUSIONS: Our presented results probably reflect the limited experience of general neurologists in the evaluation of parkinsonian syndromes and tremor. The use of SPECT-DaTSCAN by non-movement disorders specialists is associated with a significant risk of overuse of this tool. To minimise this risk, the skills of general neurologists in diagnosing parkinsonian and tremor syndromes should be improved. Moreover, patients should be provided with access to movement disorders specialists.

The symptoms asymmetry of drug-induced parkinsonism is not related to nigrostriatal cell degeneration: a SPECT-DaTSCAN study.

AIM: Drug-induced parkinsonism (DIP) is the most common form of parkinsonism after Parkinson's disease (PD) itself. It has been widely believed that DIP is characterised by symmetry of symptoms. Studies of patients with DIP in whom PD had been ruled out by SPECT-DaTSCAN have shown that symptom asymmetry is a common element of DIP clinical presentation. The aim of our study was to determine whether the asymmetry of symptoms in DIP is related to any abnormality within the presynaptic part of the nigrostriatal dopaminergic system. MATERIALS AND METHODS: Eleven patients with the diagnosis of DIP and asymmetric symptoms were studied. Their individual SPECT-DaTSCANs were normal. Indices calculated for the whole group of radiotracer uptake in the whole striatum, putamen and caudate contralateral to more severe DIP symptoms were compared to values obtained in the opposite hemisphere. RESULTS: We did not find significant differences in radiotracer uptake in structures contralateral to more severe clinical symptoms when compared to the homolateral hemisphere. CONCLUSIONS: Our results have not confirmed the presence of a presynaptic nigrostriatal deficit which could be related to asymmetry of DIP. The factors responsible for the asymmetry of DIP symptoms should be sought in the postsynaptic part of the nigrostriatal dopaminergic system.

[The applicability of 123I-FP-CIT SPECT dopamine transporter imaging in clinical practice]. / A 123I-FP-CIT SPECT dopamin transzporter képalkotás jelentosége a klinikai gyakorlatban.

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.

Extraction, selection and comparison of features for an effective automated computer-aided diagnosis of Parkinson's disease based on [123I]FP-CIT SPECT images.

PURPOSE: This work aimed to assess the potential of a set of features extracted from [123I]FP-CIT SPECT brain images to be used in the computer-aided "in vivo" confirmation of dopaminergic degeneration and therefore to assist clinical decision to diagnose Parkinson's disease. METHODS: Seven features were computed from each brain hemisphere: five standard features related to uptake ratios on the striatum and two features related to the estimated volume and length of the striatal region with normal uptake. The features were tested on a dataset of 652 [123I]FP-CIT SPECT brain images from the Parkinson's Progression Markers Initiative. The discrimination capacities of each feature individually and groups of features were assessed using three different machine learning techniques: support vector machines (SVM), k-nearest neighbors and logistic regression. RESULTS: Cross-validation results based on SVM have shown that, individually, the features that generated the highest accuracies were the length of the striatal region (96.5%), the putaminal binding potential (95.4%) and the striatal binding potential (93.9%) with no statistically significant differences among them. The highest classification accuracy was obtained using all features simultaneously (accuracy 97.9%, sensitivity 98% and specificity 97.6%). Generally, slightly better results were obtained using the SVM with no statistically significant difference to the other classifiers for most of the features. CONCLUSIONS: The length of the striatal region uptake is clinically useful and highly valuable to confirm dopaminergic degeneration "in vivo" as an aid to the diagnosis of Parkinson's disease. It compares fairly well to the standard uptake ratio-based features, reaching, at least, similar accuracies and is easier to obtain automatically. Thus, we propose its day to day clinical use, jointly with the uptake ratio-based features, in the computer-aided diagnosis of dopaminergic degeneration in Parkinson's disease.

Semi-quantitative dopamine transporter standardized uptake value in comparison with conventional specific binding ratio in [123I] FP-CIT single-photon emission computed tomography (DaTscan).

PURPOSE: We developed a new analytical method to quantify the dopamine transporter (DAT) radiation dose in the striatum on [123I] FP-CIT single-photon emission computed tomography (SPECT). This method is based on the dopamine transporter standardized uptake value (DaTSUV). The purpose of this study was to compare DaTSUV with the classical specific binding ratio (SBR) in the discrimination of dopaminergic neurodegenerative diseases (dNDD) from non-dNDD. METHOD: Seventy-seven consecutive patients who underwent DaTscan were included. Patients were divided into a dNDD group (n = 44; 24 men, 20 women; median age 73 years) and a non-dNDD group (n = 33; 14 men, 19 women; median age 75 years) based on their clinical diagnoses. The relationship between each method was evaluated by Pearson's correlation coefficient. Differences in SBR and DaTSUV in each group were evaluated by t test. Pairwise comparison of receiver operating characteristic (ROC) curve analysis was performed to compare the discriminating abilities of each method according to the standard error of the area under the curve (AUC). A value of p < 0.05 was considered statistically significant. RESULT: There was a significant strong correlation between DaTSUV and SBR (r = 0.910 [95% CI = 0.862-0.942], p < 0.001). The dNDD group showed significantly lower SBR (3.48 [1.25-7.91] vs 6.58 [3.81-11.1], p < 0.001) and DaTSUV (4.91 [1.59-13.6] vs 8.61 [2.29-15.6], p < 0.001) than the non-dNDD group. The discriminating ability of SBR (AUC = 0.918) was significantly higher than that of DaTSUV (AUC = 0.838, p = 0.0176). CONCLUSION: DaTSUV has a good correlation with SBR, but it could not exceed SBR for discriminating dNDD from non-dNDD.

Voxel-based logistic analysis of PPMI control and Parkinson's disease DaTscans.

A comprehensive analysis of the Parkinson's Progression Markers Initiative (PPMI) Dopamine Transporter Single Photon Emission Computed Tomography (DaTscan) images is carried out using a voxel-based logistic lasso model. The model reveals that sub-regional voxels in the caudate, the putamen, as well as in the globus pallidus are informative for classifying images into control and PD classes. Further, a new technique called logistic component analysis is developed. This technique reveals that intra-population differences in dopamine transporter concentration and imperfect normalization are significant factors influencing logistic analysis. The interactions with handedness, sex, and age are also evaluated.

Is nigrostriatal dopaminergic deficit necessary for Holmes tremor to develop? The DaTSCAN and IBZM SPECT study.

Holmes's tremor (HT) is assumed to be the result of coexistence of nigrostriatal dopaminergic system impairment and the lesion of cerebello-thalamic pathways. It was suggested that dopaminergic deficiency is responsible for rest tremor, and lack of compensatory cerebellar function leads to spill of tremor into voluntary movements. Cases of HT with and without abnormalities of the presynaptic part of dopaminergic nigrostriatal were published and these findings raised the question of possibility of the postsynaptic lesion. Three patients with HT diagnosed according to criteria of Consensus Statement on Tremor were studied. In all of them SPECT imaging with ligands of presynaptic (I 123-FP CIT-DaTSCAN) and postsynaptic (I 123-iodobenzamide-IBZM) nigrostriatal dopaminergic neurons was performed. Indices of uptake in caudate and putamen normalized to nonspecific uptake in occipital cortex and indices of asymmetry for each whole striatum as well as for putamen and caudate separately were calculated. SPECT studies did not reveal asymmetry of DaTSCAN and IBZM binding in striatum in all studied subjects. The current clinical diagnostic criteria of HT are presumably insufficiently specific and when using them we identify patients both with and without the involvement of dopaminergic system. These two groups may represent tremor disorders of similar phenomenology but of different pathomechanism.