Hebrew University develops method to diagnose early-stage Parkinson’s disease

30,000 Israelis and 10 million people worldwide live with the disorder.

 MRI images used for automatic detection of microstructural changes in early-stage Parkinson’s Disease (PD) patients. Marked in yellow are areas in the putamen where PD patients show tissue damage, compared to healthy controls. (photo credit: MEZER LAB/HEBREW UNIVERSITY)
MRI images used for automatic detection of microstructural changes in early-stage Parkinson’s Disease (PD) patients. Marked in yellow are areas in the putamen where PD patients show tissue damage, compared to healthy controls.
(photo credit: MEZER LAB/HEBREW UNIVERSITY)

Parkinson’s disease (PD) – a progressive and debilitating disease of the brain that eventually halts patients’ ability to walk and even to talk – is complex and, in the early stages, impossible to diagnose.

More than 10 million people around the world and 30,000 in Israel are living with PD, and 300,000 people of all ages are estimated to be at risk because they carry a genetic mutation or for other reasons. The incidence of Parkinson’s disease increases with age. Only four percent of PD patients are diagnosed before age 50.

The usual method of visualizing brain structure is by using magnetic resonance imaging (MRI), but it is not sensitive enough to reveal the biological changes that take place in the brains of PD patients. At present, it is used mostly to rule out other possible diagnoses.

“Israel’s high rate of genetic Parkinson’s provides an opportunity to make Israel a global hub for research and development, and some earlier breakthroughs in Parkinson’s research and treatment came out of Israeli labs, according to Prof. Nir Giladi, who co-directs Tel Aviv University’s Center for the Prevention and Treatment of Parkinson’s Disease.

But now, researchers at the Hebrew University of Jerusalem (HU), led by Prof. Aviv Mezer, have discovered that the cellular changes in PD could be revealed by adapting a related technique, known as quantitative MRI (qMRI). Their method has enabled them to look at microstructures within the part of the deep brain known as the striatum – an organ which is known to deteriorate during the progress of Parkinson’s disease.

 Israelis walking in front of the entrance to the Hebrew University of Jerusalem (credit: MARC ISRAEL SELLEM/THE JERUSALEM POST) Israelis walking in front of the entrance to the Hebrew University of Jerusalem (credit: MARC ISRAEL SELLEM/THE JERUSALEM POST)

The analysis

Using a novel method of analysis, developed by Mezer’s doctoral student Elior Drori, biological changes in the cellar tissue of the striatum were clearly revealed. They were also able to show that these changes were connected with the early stages of PD and patients’ movement dysfunction. Their findings have just been published in Science Advances under the title “Microstructural Gradients of the Human Striatum in Normal Aging and Parkinson’s Disease.”

qMRI achieves its sensitivity by taking several MRI images using different excitation energies, which is rather like taking the same photograph in different lighting. The HU researchers were able to use their qMRI analysis to reveal changes in the tissue structure within distinct regions of the striatum.

The structural sensitivity of these measurements could only have been previously achieved in laboratories examining the brain cells of patients after death in an autopsy, which is not an ideal way to detect early disease or monitor the efficacy of a drug.

“When you don’t have measurements, you don’t know what is normal and what is abnormal brain structure, and what is changing during the progress of the disease,” explained Mezer. “The new information will facilitate early diagnosis of the disease and provide ‘markers’ for monitoring the efficacy of future drug therapies. What we have discovered,” he continued “is the tip of the iceberg.”

“When you don’t have measurements, you don’t know what is normal and what is abnormal brain structure, and what is changing during the progress of the disease.”

Prof. Aviv Mezer

They will now extend their technique to investigate microstructural changes in other regions of the brain. The team members are also developing qMRI into a tool that can be used in a clinical setting. Mezer anticipates this will happen in about three to five years.

Drori further suggests that this type of analysis will enable identification of subgroups within the population suffering from PD, some of whom may respond differently to some drugs than others. Ultimately, he sees this analysis “leading to personalized treatment, allowing future discoveries of drugs, with each person receiving the most appropriate drug.”