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Linda Al-Hassany

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Applying mathematical techniques to address a medical challenge

Bachelor thesis (2025) - C.T.T. Zheng, C. Vuik, M. Keijzer, Linda Al-Hassany, Antoinette Maassen-Van den Brink

Migraine is a prevalent, complex neurovascular disorder that mainly affects women. The exact pathophysiology of migraine is unclear, but research indicates that activation of the trigeminal nerve in the trigeminovascular system causes release of calcitonin gene-related peptide (CGRP), which triggers migraine attacks. Additionally, nitric oxide (NO) contributes to the pathophysiology of migraine headaches. Research suggests that migraine patients have an increased risk of cardiovascular disease. Over the past decades, non-invasive techniques, like Laser Doppler imaging (LDI) and Laser speckle contrast imaging (LSCI) have been developed for imaging tissue perfusion, which are valuable tools for investigating the underlying causes for this increased risk and facilitates the study of blood perfusion. The Erasmus Medical Center (Erasmus MC) used these techniques to perform measurements of the microvascular blood flow in the forearm as a measure of the microvasculature of women with and without migraine. This study, also known as the VASCULAR-study, focused on three regions of interest (ROIs), where NO was inhibited using iontophoresis with L-NMMA and neuropeptides were blocked using EMLA cream. The last ROI served as the control region. The measurements also consisted of three different phases: baseline, peak and plateau phase. Studies have shown that distinct biological mechanisms in the body can be linked to different frequency intervals and therefore, Fourier analysis (FA) and wavelet analysis (WA) were used to transform the VASCULAR-study data into the frequency domain. Two preliminary studies used FA to perform the transformation. This study primarily focused on WA. The research question is as follows: Does wavelet analysis (WA) of the VASCULAR-study data yield more insights than Fourier analysis (FA) into blood flow measurements in women, particularly in examining the role of nitric oxide (NO) and calcitonin gene-related peptide (CGRP) in the microvasculature among women with and without migraine? To address the research question, WA was conducted using the complex Morlet wavelet. Relative energy density was used as a quantitative metric to compare the group of women with migraine with the group of women without migraine. Relative energy density was also calculated for the results using FA. Statistical significance was assessed using p-values, where p-values below 0.05 were considered significant. The Mann-Whitney U-Test and the Wilcoxon Signed Rank Test were used to calculate the p-values. Significant differences between women without migraine and women with migraine were primarily found in respiratory and endothelial activity for both WA and FA. Women with migraine showed higher respiratory activity in regions where NO was inhibited, for both WA and FA. Although WA and FA revealed many similar results in the VASCULAR-study dataset, there were also some differences. These differences were mainly observed in endothelial activity, in the ROI where NO was inhibited. FA revealed significantly higher values in activity for women without migraine in both NO-independent and NO-dependent endothelial activity. Furthermore, using the time-frequency localization capability of the WA, it showed significantly higher activity in women with migraine between the peak and plateau phase.

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Bachelor thesis (2023) - Nisharani Agnihotri, C. Vuik, M. Keijzer, Linda Al-Hassany, Antoinette Maassen-Van den Brink
Erasmus MC is conducting a study on the increased risk of cardiovascular disease in women who have migraine. For this purpose, 50 healthy women and 50 women with migraine in age category of 40-60 years were compared using measurements of their dermal blood flow.
These measurements are done using two different imaging devices: Laser Speckle Imaging and Laser Doppler Imaging. The result is a recording of the fluctuations in the dermal blood flow over a time period influenced by circumstances and various mechanisms and consists of signal like curves. Erasmus MC have processed these measurements and obtained results. However, they are interested in whether applying Fourier Transform could offer additional insights or new (perhaps faster) methods to process the measurements.
The signal like curves can possibly be decomposed into sine and cosine waves using Fourier Transform. The result of the Fourier Transform consists of a visualisation of the intensity of the various components of such a waveform/curve. Based on that, it is possible to estimate the contribution of the mechanisms to blood perfusion. Existing literature and previous studies provide frequency intervals related to several mechanisms that influence the dermal blood flow.
This thesis will research to what extent the mechanisms contribute to the dermal blood flow across the different phases and how their behaviour differs when the circumstances for the measurement are adjusted. Perhaps there are behaviours that are instantly recognizable across all patients. An interesting question to answer would be whether it is possible to directly visualise the risk groups. ...