Background

Parkinson's disease context

The neurobiology, the clinical picture, the therapeutic landscape as of 2025, and the 2023 study on patient-specific striatal binding ratio (SBR) extraction that started the program's imaging line of work.

Neurobiology in focus

Parkinson's disease begins with degeneration of dopaminergic neurons within the substantia nigra pars compacta, but the cascade quickly recruits cholinergic and cerebello-thalamo-cortical networks. These circuit-wide disruptions explain why gait, balance, cognition, and autonomic regulation can deteriorate even when motor tremor appears well controlled.

Protein misfolding, mitochondrial stress, lysosomal dysfunction, and immune signaling, including genes such as BST1, SYT11, TMEM175, and GRN, activate selective vulnerability across the basal ganglia. Our models incorporate these molecular signatures alongside imaging-derived biomarkers.

DaTSCAN and MRI overlay highlighting striatal pathways.

Clinical manifestations we model

Motor domains

Nigrostriatal dopamine deficit drives bradykinesia, rigidity, and resting tremor.
Network-level changes produce medication-refractory tremor and dyskinesia.
Cholinergic degeneration contributes to freezing of gait, postural instability, and falls.

Non-motor domains

Cognitive fluctuations and hallucinations reflect cholinergic and cortical involvement.
Mood, anxiety, and sleep disturbances stem from monoaminergic dysregulation beyond dopamine.
Autonomic failure drives orthostatic hypotension, sialorrhea, constipation, and urinary urgency.

Therapeutic landscape as of 2025

Dopaminergic strategies

Early-stage motor symptoms often respond to levodopa/carbidopa (immediate or extended release), dopamine agonists, and MAO-B inhibitors such as rasagiline, selegiline, or safinamide. Rytary® smooths motor control, while add-on safinamide extends “ON” time.

Advanced delivery options

Complex fluctuations may require enteral Duopa® gel, continuous levodopa/carbidopa infusion (Vyalev™, FDA cleared 2024), or subcutaneous apomorphine (Onapgo™, 2025). Neuromodulation via deep brain stimulation (STN/GPi) remains a cornerstone.

Emerging procedural care

MR-guided focused ultrasound has progressed from unilateral to staged bilateral procedures, with FDA clearance in July 2025 for select centers. It offers incisionless tremor relief and reduced dyskinesia for advanced disease.

Non-motor management

SSRIs/SNRIs effectively address depression and anxiety without worsening motor scores. Melatonin or clonazepam mitigate REM sleep behavior disorder, while tailored tapering of dopamine agonists manages impulse-control disorders alongside behavioral therapy.

Autonomic support

Orthostatic hypotension starts with hydration, salt, and compression, escalating to droxidopa or midodrine. Botulinum toxin injections relieve sialorrhea, polyethylene glycol is the preferred first-line osmotic laxative, and mirabegron offers bladder control with minimal cognitive burden.

These interventions are powerful, yet they are prescribed largely on population averages. Our multimodal approach learns which combination, sequence, and timing work best for each individual patient profile.

2023 study

Quick and efficient extraction of patient-specific SBR ratios

The program's imaging thrust grew out of a 2023 study that replaced hours of manual striatal segmentation with SegFormer masks generated in minutes, then used them to extract patient-specific striatal binding ratios from DaTSCAN. The write-up is in four parts:

Reference notebooks and reports are listed on the resources page.