To investigate whether 7T 31P magnetic resonance spectroscopy (MRS) provides an objective method to assess metabolic changes in response to ischemia in calf muscles of patients with critical limb ischemia (CLI) compared to healthy controls.Research…
ID
Source
Brief title
Condition
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Ad 1: Fifteen healthy controls will be subjected to a short period of
unilateral arterial occlusion of the leg by supersystolic compression of the
lower extremity arteries with an inflatable cuff. 7T 31P MRS will be performed
before, during and after occlusion. Pi/ATP and PCr/ATP-ratios and pH will be
compared between timepoints.
The fifteen healthy controls will be scanned on a separate occasion and results
will be compared to test the test-retest reliability of the method.
Ad 2: Fifteen patients with proven chronic infra-popliteal CLI, who are not
candidates for surgical or radiological revascularization will undergo 7T 31P
MRS without applying arterial compression. Pi/ATP and PCr/ATP-ratios and pH
will be determined and compared to healthy controls with and without ischemia.
Secondary outcome
NA
Background summary
Peripheral arterial disease (PAD) is a common cause of disability and
mortality. In the last decade, therapies focusing on therapeutic
neovascularization in cardiovascular diseases, ie the stimulation of new vessel
formation have raised much interest. A drawback in studies that focus on such
therapies is the lack of a valid and reliable objective perfusion measurement
to evaluate the effects of such therapies. The ultra high magnetic field of a 7
Tesla (7T) MRI potentially provides the means for non-invasive assessment of
functional and metabolic processes in the ischemic calf muscles of these
patients. Phosphorus (31P) spectroscopy measures the tissue content of
different 31P containing molecules that are involved in energy metabolism of
the cells.
Study objective
To investigate whether 7T 31P magnetic resonance spectroscopy (MRS) provides an
objective method to assess metabolic changes in response to ischemia in calf
muscles of patients with critical limb ischemia (CLI) compared to healthy
controls.
Research questions:
(1) Can 7T 31P MRS determine metabolic changes in the calf muscle of healthy
controls in response to short-lived lower limb ischemia assessed as changes in
inorganic phosphate (Pi)/ Adenosine triphosphate (ATP) and phophocreatine
(PCr)/ATP-ratios, and tissue pH?
(2) Can 7T 31P MRS identify differences in the spectroscopic profile in
patients with chronic CLI as compared to healthy controls with and without
ischemia?
Study design
Non-interventional, cross-sectional, study.
Study burden and risks
Patients will undergo a one hour pre-tested 7T MRI protocol. No contrast agents
or other pharmacological substance will be administered. Yearly, more than 60
million studies are performed on 1.5T MRI platforms without significant
negative side-effects. Up till now the amount of imaging studies performed on 7
or 8T MRI scanners is much smaller, but far over 1000 subjects have been
scanned without clinical significant adverse effects.
Heidelberglaan 100
3584 CX Utrecht
NL
Heidelberglaan 100
3584 CX Utrecht
NL
Listed location countries
Age
Inclusion criteria
Inclusion criteria:
- Age > 18 years;
- Severe infra-popliteal PAOD (Fontaine class III and / or IV); Fontaine III: persistent, recurring rest pain requiring analgesia; Fontaine IV: non-healing ulcers present for > 4 weeks without evidence of improvement in response to conventional therapies
- Ankle brachial index < 0.6 or unreliable (non-compressible or not in proportion to the Fontaine classification);
- Written informed consent. ;The criteria apply to patients. Healthy controls may be included if they are above 18 years and have no signs of PAOD.
Exclusion criteria
Exclusion criteria:
-Pregnancy
-Ineligible for scanning in the 7T MRI: subjects with cardiac pacemakers, claustrophobia, or metallic objects, i.e. stents, surgical clips etc. and all patients with bio-implants not explicitly indicated as safe to 7T MRI (see: mrisafety.com).;The abovementioned criteria apply to both patients and healthy controls.
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 | NL33906.041.10 |