Parkinson’s Disease & Multiple System Atrophy Imaging for Clinical Trials​

Biomarkers for Parkinsons disease encompass a range of advanced imaging techniques that provide insight into different aspects of disease pathology. DatScan SPECT imaging is widely used to assess dopamine transporter density. Structural MRI plays a critical role in for detecting brain atrophy, which can help differentiate Parkinsonian syndromes; for instance, cerebellar atrophy is characteristic of multiple system atrophy with cerebellar features (MSA-C), while tracking basal ganglia volume can provide insights into disease progression in Parkinson's disease (PD). FDG PET imaging offers another important tool by measuring regional cerebral glucose metabolism, which can reveal characteristic metabolic patterns in PD and related disorders, such as hypometabolism in the posterior parietal and occipital cortices seen in Dementia with Lewy bodies (DLB). Neuromelanin-sensitive MRI provides a non-invasive method to visualize neuromelanin content within the substantia nigra, a region that undergoes significant degeneration in PD, offering a promising marker for early diagnosis. Diffusion MRI is particularly useful in assessing microstructural changes in white matter tracts, with alterations in the nigrostriatal pathways providing additional diagnostic clues and aiding in the differentiation of PD from atypical Parkinsonian syndromes. Together, these imaging modalities provide a comprehensive approach to assessing Parkinson's disease, facilitating early diagnosis, differential diagnosis, and monitoring of disease progression. 

DaTscan, also known as Ioflupane I 123 injection, is a radiopharmaceutical agent used in single-photon emission computed tomography (SPECT) imaging of the brain. It is specifically designed to assess the integrity of dopamine transporters. DaTscan is utilized in Parkinson's disease studies to aid in assessing patient eligibility by accurately identifying Parkinsonian populations.​ In addition to its diagnostic role, DaTscan SPECT is also valuable in monitoring disease progression by tracking the gradual decline in dopamine transporter density, which reflects ongoing neurodegeneration in the nigrostriatal pathway. This imaging modality is increasingly employed in clinical trials to evaluate the therapeutic effects of potential treatments, providing an objective biomarker to assess whether interventions can slow or stabilize dopaminergic degeneration. By offering quantitative insights into changes in dopamine transporter density over time, DaTscan SPECT plays a pivotal role in both patient stratification and outcome assessment in Parkinson's disease research. 

Biospective has utilized various imaging modalities in clinical trials for Parkinson's disease, including MRI, AV133 PET, and DatScan SPECT, and the cutting edge Neuromelanin imaging to assess disease progression and treatment effects. ​  

Neuromelanin imaging is a specialized MRI technique that allows for the visualization of neuromelanin-containing neurons in the substantia nigra and locus coeruleus, offering insights into Parkinson's disease pathology. High spatial resolution midbrain and pons images enable the visualization of neuromelanin-containing structures with high contrast and detail, enhancing the detection of Parkinsonian-related changes. 

For obtaining neuromelanin images, the preferred scan type includes turbo spin echo (TSE) and gradient echo (GRE) sequences due to their superior imaging capabilities and suitability for neuromelanin visualization. 

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Biomarker: a measurable indicator of a biological state or condition. Biomarkers are often used in medicine and research to detect or monitor the presence, progress, or severity of a disease, as well as to assess the effectiveness of a treatment.   

Brain Atrophy: reduction in volume or thickness of the entire brain or regions of the brain.    

Dopamine: a catecholamine neurotransmitter that plays key roles in the nervous system. 

DaTscan SPECT: a single-photon emission computed tomography (SPECT) imaging method using the [123I]FP-CIT tracer to visualize dopamine transporter (DAT) availability in the brain. 

Magnetic Resonance Imaging (MRI): a non-invasive imaging modality that uses magnetic fields and radiofrequency (RF) pulses to generate images.  

Multiple System Atrophy (MSA): a sporadic, rapidly progressive, adult-onset neurodegenerative disorder that manifests clinically as a diverse combination of parkinsonism (MSA-P), cerebellar ataxia (MSA-C), and autonomic dysfunction 

Neurodegeneration: a complex, multifactorial process resulting in the loss of neurons.   

Neuroimaging: the process of generating images of structural and functional components within the nervous system, utilizing such techniques as MRI and PET imaging.  

Parkinson's Disease (PD): a neurodegenerative disease that is characterized by: (a) movement-related (motor) symptoms, including resting tremor, bradykinesia, rigidity, and postural instability, related to the loss of dopaminergic neurons in the substantia nigra; and (b) non-motor symptoms including anxiety, depression, apathy, hallucinations, constipation, orthostatic hypotension, sleep disorders, hyposmia/anosmia, and cognitive impairment.  ​  

Positron Emission Tomography (PET): a non-invasive imaging technique used in medical diagnostics and research to visualize and measure metabolic and molecular processes in the body. PET scans involve the use of a small amount of injected radioactive tracer. The tracer emissions are collected by PET scanner detectors which uses them to create detailed three-dimensional images of the tracer distribution within the body. PET scans are often combined with computed tomography (CT) or magnetic resonance imaging (MRI) to provide both metabolic/molecular and anatomical information, enhancing the accuracy of diagnosis and treatment planning.   

Region-of-Interest (ROI): a specific subset of data identified within an image. For volumetric analysis, the ROIs correspond to neuroanatomical structures and parcellated features.    

Single-Photon Emission Computed Tomography (SPECT): a nuclear imaging technique that uses gamma ray–emitting tracers and a rotating gamma camera to produce 3D images providing functional information about blood flow, metabolism, or receptor binding. As opposed to PET, SPECT detects single photons rather than coincident pairs. SPECT produces lower resolution images, but relies on tracers with a longer half-life which can have logistical advantages. 

VMAT-2 (Vesicular Monoamine Transporter 2): a protein responsible for packaging monoamines (including dopamine) into presynaptic vesicles.