The main objective of this pilot study is to determine if 31P MRS and BOLD-MRI or 1H MRS can be used as diagnostic tests to discriminate between ischemic muscle and normally oxygenized muscle and to assess their reproducibility.
ID
Source
Brief title
Condition
- Muscle disorders
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
31P MRS:
- PCr recovery rate after exercise or induced ischemia
- time to lowest PCr concentration after exercise or induced ischemia
BOLD-MRI:
- signal intensity (SI) after exercise or induced ischemia
- time to peak (TTP) after exercise or induced ischemia
1H MRS:
- decay or loss of deoxymyoglobine signal after exercise or induced ischemia
intraclass coefficient (ICC) for all the abovementioned parameters.
Secondary outcome
- to demonstrate a correlation between 31P MRS and BOLD-MRI and/or 1H MRS
- to demonstrate a correlation between 31P MRS and clinical symptoms
- to demonstrate a correlation between BOLD-MRI or 1H MRS and clinical symptoms
- to derive a dynamic pH-curve from the inorganic phosphate peak detected by
dynamic 31P MRS and correlate these changes with clinical symptoms (pain)
Background summary
Peripheral arterial disease, like exertional and rest pain of the legs, is
caused by atherosclerosis. This chronic and progressive disease eventually
results in lipid-rich atherosclerotic plaques in the arterial wall that narrow
the lumen and thereby causing reduced blood flow to distal tissues. Exertional
and rest pain of the legs, persistent skin infections and ischemic tissue loss
are disabling symptoms of this process and may necessitate limb amputation. In
current clinical practice diagnostic tests are informative about lumen size,
blood pressure and blood flow, which is only useful to demonstrate end stage
disease. In addition, their diagnostic reliability and reproducibility are
limited and they did not affect clinical outcome. They also lack information
about tissue oxygenation. Novel imaging modalities like 31P MRS, BOLD-MRI and
1H MRS are very promising because they provide noninvasive, functional, dynamic
and in situ information about tissue oxygenation. Because these imaging
modalities are acquired with MR, detailed anatomical images can be obtained as
well. These noninvasive, molecular imaging techniques have the potential to (1)
replace current diagnostic tests; (2) demonstrate a clear and univocal relation
between narrowing of arterial lumen and clinical symptoms of peripheral
arterial disease; (3) quantify the functional consequences of narrowing of
arterial lumen and an impaired oxygen supply to distal tissues. In addition,
they can contribute to new insights in pathophysiology of atherosclerosis.
Study objective
The main objective of this pilot study is to determine if 31P MRS and BOLD-MRI
or 1H MRS can be used as diagnostic tests to discriminate between ischemic
muscle and normally oxygenized muscle and to assess their reproducibility.
Study design
This is a pilot study designed as a single center observational case-control
study. After screening for eligibility all subjects will undergo cardiovascular
risk assessment. Subsequently, all subjects will undergo 31P MRS and BOLD-MRI
or 1H MRS of the lower leg in a single scan session in our Philips Ingenia 3
Tesla MRI. The scan session will be repeated in healthy subjects for
reproducibility and patients with peripheral arterial disease planned for
intervention will undergo a second scan session after intervention.
Study burden and risks
The maximum estimated time patients spend at the AMC will be two visits of 1,5
hour. The risk involved while participating in this pilot study are very low.
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
patients:
- ongoing reversible exertional pain in the lower right and/or left leg (Fontaine 2b)
- ongoing rest pain in the lower right and/or left leg (Fontaine 3) (if possible)
- age 40 years or older;healthy volunteers:
- no history of cardiovascular disease
- no cardiovascular risk factors
Exclusion criteria
for all groups:
- history of muscular diseases
- diabetes mellitus
- metabolic diseases
- (locomotor) neurologic abnormalities or diseases
- known systemic disorders
- standard contraindications for MRI;healthy controls: use of any cardiovascular medication, including but not limited to lipid-lowering therapy, antihypertensive drugs, antidiabetic drugs, platelet aggregation inhibitors and anticoagulants
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL52059.018.14 |