Unsupervised machine learning identifies clinically relevant patterns of CSF dynamic dysfunction in normal pressure hydrocephalus

Background

Idiopathic normal pressure hydrocephalus (iNPH) is a common and debilitating condition whose diagnosis is made challenging due to the unspecific and common clinical presentation. The aim of our study was to determine if data driven patterns of cerebrospinal fluid (CSF) distribution can be used to predict iNPH diagnosis and response to treatment.

Methods

We established a cohort of iNPH patients and age/sex-matched controls. We used Non-negative Matrix Factorization (NMF) on CSF probability maps from segmentation of T1-weighted MRI to obtain patterns or components of CSF distribution across participants and a load on each component in each participant. Visual assessment of morphologic phenotype was performed by a neuroradiologist, and clinical symptom improvement was assessed via retrospective chart review. We used the NMF component loads to predict diagnosis and clinical outcome after ventriculoperitoneal shunt placement for treatment of iNPH. Similar models were developed using manual Evan’s index and callosal angle measurements.

Results

We included 98 iNPH patients and 98 controls split into test (20 %) and train (80 %) sets. The optimal NMF decomposition identified 7 patterns of CSF distribution in our cohort. Accuracy for predicting a clinical diagnosis of iNPH using the automated NMF model was 96 %/97 % in the train/test sets, which was similar to the performance of the manual measure models (92 %/97 %). Visualizing the voxels that contributed most to the NMF models revealed that the voxels most associated with a disproportionately enlarged subarachnoid space hydrocephalus (DESH) were the ones with higher probability of iNPH diagnosis. Neither NMF nor manual metrics performed well for prediction of qualitative clinical outcomes.

Conclusions

NMF-generated patterns of CSF distribution showed high accuracy in discerning individuals with iNPH from controls. The patterns most relying on DESH features showed highest potential for independently predicting NPH diagnosis. The algorithm we proposed should not be perceived as a replacement for human expertise but rather as an additional tool to assist clinicians in achieving accurate diagnoses.