TCD-Profiling Using AVERAGE. A New Technique to Evaluate Transcranial Doppler Ultrasound Flow Spectra of Subjects with Cerebral Small Vessel Disease

Background: There is an unmet need for screening methods to detect and quantify cerebral small vessel disease (SVD). Transcranial Doppler ultrasound (TCD) flow spectra of the larger intracranial arteries probably contain relevant information about the microcirculation. However, it has not yet been possible to exploit this information as a valuable biomarker. Methods: We developed a technique to generate normalized and averaged flow spectra during middle cerebral artery Doppler ultrasound examinations. Second, acceleration curves were calculated, and the absolute amount of the maximum positive and negative acceleration was calculated. Findings were termed ‘TCD-profiling coefficient' (TPC). Validation study: we applied this noninvasive method to 5 young adults for reproducibility. Degenerative microangiopathy study: we also tested this new technique in 30 elderly subjects: 15 free of symptoms but with MRI-verified presence of cerebral SVD, and 15 healthy controls. SVD severity was graded according to a predefined score. Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) study: TPC values of 10 CADASIL patients were compared with those of 10 healthy controls. Pulse wave analysis and local measurements of carotid stiffness were also performed. CADASIL patients were tested for cognitive impairment with the Montreal Cognitive Assessment scale. White matter and basal ganglia lesions in their cerebral MRI were evaluated according to the Wahlund score. Results: Validation study: the technique delivered reproducible results. Degenerative microangiopathy study: patients with SVD had significantly larger TPCs compared with controls (SVD: 2,132; IQR 1,960-2,343 %/s vs. controls: 1,935; IQR 1,782-2,050 %/s, p = 0.01). TPC values of subjects with SVD significantly correlated with SVD severity scores (R = 0.58, n = 15, p < 0.05). CADASIL study: TPC values of CADASIL patients were significantly higher than values of the controls (CADASIL: 2,504; IQR 2,308-2,930 %/s vs. controls 2,084; 1,839-2,241 %/s, p = 0.008), and also significantly higher than the TPC values of the patients with SVD from the degenerative microangiopathy study (p = 0.007). CADASIL patients had significantly worse cognitive test results than healthy controls. Conclusion: TCD-profiling detects impairment of the cerebral microcirculatory state. The suitability of the TCD-profiling for the evaluation of cerebral microangiopathy was confirmed.