Test of Reproducibility of [15O]H20-PET Assessment of Brain Perfusion

Summary

In the aging population, ischemic heart disease, stroke and dementia are increasingly prevalent. Diagnosis and treatment of the former two i.e., large-vessel coronary heart disease and endovascular thrombectomy of the brain in relation to stroke have improved significantly. Yet, the majority of elderly patients with ischemic heart disease do not have large-vessel heart disease and it seems that small vessel disease (SVD) may explain a large fraction of these cases as well as the cardiovascular morbidity in the elderly. Hence, the current development in diagnostics and treatments of ischemic heart disease does not address the most common subtype of ischemic disease seen in elderly patients.

It has been suggested that SVD is part of a multisystem disorder and several systematic reviews have addressed the hypothesis of a potential link between small vessel disease of the heart, brain, and kidneys. Cerebral SVD is prevalent in the aging population causing cognitive impairment, dementia, and an increased risk of stroke, and cerebral hypoperfusion is an acknowledged cause of vascular dementia and a possible cause of Alzheimer's disease. Further, cognitive impairment within multiple cognitive domains is highly prevalent in heart failure and is associated to an increased risk of dementia. The link between heart failure and dementia may be due to multisystem SVD, although a direct link between the two is possible.

Among other known risk factors such as age, hypertension, and female sex, diabetes is a major cause of SVD and is linked to coronary heart disease as well as cognitive impairment. The diagnosis of cerebral SVD relies on MRI detecting infarctions, haemorrhages, microbleeds and ischemic white matter changes, i.e. Fazekas score. In contrast, perfusion PET is used to image myocardial perfusion in patients with coronary SVD; and coronary SVD is recognized as a part of the pathophysiology in angina, coronary artery disease, and heart failure. Perfusion PET before and after adenosine-induced vasodilation allows for measuring, the myocardial flow reserve (MFR), i.e. perfusion capacity, which in the absence of regional perfusion defects, is a measure of coronary SVD. Prof. Eva Prescott have recently shown that reduced MFR obtained by 82Rb PET is a strong predictor of future microvascular events and all-cause mortality.

Exercise is well known to improve cognitive health but professor Carl-Johan Boraxbekk has shown that the effect on cognitive performance may be dependent on the initial cerebrovascular status, as patients with moderate to severe white matter changes did not improve after a 6 months physical activation intervention in contrast to patients with mild changes. Yet, it is possible to improve brain function in diabetic patients through either dietary or exercise interventions.

Systemic SVD is measured as cerebral SVD (reduced brain perfusion during acetazolamide-induced vasodilation) and coronary SVD (reduced heart perfusion during adenosine-induced vasodilation). The researchers anticipate that patients with type 2 dabetes have reduced perfusion capacity of the brain and heart correlating to reduced cognition and cardiorespiratory fitness (VO2-max).

Conditions

• Microvascular Disease
• Microvascular Complications
• Diabetes Mellitus Type 2
• Cerebral Hypoperfusion
• Dementia

Interventions

DIAGNOSTIC_TEST

PET

PET imaging will be performed with a Discovery 710 PET/CT scanner (GE Healthcare, Milwaukee, WI, USA). Two 5-minute PET recordings will be performed of each subject within a single scanning session of 70 min. One 5-minute scan is conducted of the brain in rest. \[15O\]H2O, is produced on-site (GENtrace, GE, Uppsala, Sweden), and 600 MBq \[15O\]H2O is intravenously injected by an automatic Hidex Radiowater Generator (Hidex, Turku, Finland). To induce brain vasodilation, 1 g of acetazolamide is infused over 5 min and 15 min later the brain is scanned. Cerebral perfusion is calculated using PMOD software (PMOD Technologies, Switzerland).

Sponsors & Collaborators

• Danish Cardiovascular Academy

  collaborator UNKNOWN

• Bispebjerg Hospital

  collaborator OTHER

• The Dagmar Marshall Foundation

  collaborator OTHER

• Steno Diabetes Center Copenhagen

  collaborator OTHER

• University Hospital Bispebjerg and Frederiksberg

  lead OTHER

Principal Investigators

• Thomas EHJ Primary Investigator, Medical Doctor · University Hospital Bispebjerg and Frederiksberg

Eligibility

Min Age

60 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2024-11-30

Primary Completion

2027-01-31

Completion

2027-12-31

Countries

• Denmark

Study Locations