Intraosseous Doppler Ultrasonography to Study Skeletal Physiology: Exploratory Study Before Use in Space Physiology
- Conditions
- Healthy Volunteers
- Interventions
- Device: Intraosseous ultrasonography at tibia before, during, and after a physiological vascular stimulation (venous occlusions, arterial occlusion, handgrip)
- Registration Number
- NCT06206031
- Lead Sponsor
- University Hospital, Angers
- Brief Summary
Use of intraosseous Doppler ultrasonography to study skeletal physiology ("Echo-Os Study"). Exploratory study before its use in space physiology.
Bones have a complex vascular network providing nutrients and oxygen to bone cells. The physiology of intraosseous blood circulation remains very little known to date, particularly in human. Human bone vascularization studying is very difficult because of a lack of simple tools for functional exploration of bone vascular perfusion. For blood flow studies, ultrasonography is best suited, allowing for dynamic non-invasive measures. Bone has until now been considered to stop ultrasound and therefore prevent any intraosseous measurements. From a physics viewpoint, bones conduct ultrasound waves well, but they are reflected differently compared to soft tissues. A specific analysis of the ultrasound returned by the bone, using specific correction factors, is therefore needed to interpret ultrasound signals, reconstruct an anatomical image, and extract physiological information. The system proposed in this study combines standard conventional low-frequency ultrasound probes with a specific analysis of ultrasound wave reflection. This system makes it possible to reconstruct an anatomical bone image and record the pulsatile signal of intraosseous vascular perfusion. The investigators will use this system to study the vascular reactivity induced by different physiological maneuvers.
This protocol proposes to study the following mechanisms of blood flow regulation at the level of tibia cortical bone: flow-mediated dilation induced by endothelium (with arterial occlusion test), vasoconstriction induced by sympathetic activation (with static handgrip test), and vasoconstriction induced by veno-arteriolar reflex (with venous occlusion test). This is a pilot study in physiology performed with healthy volunteers. This study will verify whether our intraosseous ultrasound system can properly measure physiological responses expected during these maneuvers. This protocol will also establish links between perfusion and bone architecture at tibial level.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 30
Not provided
- Any abnormality or deviation from the selection criteria identified during the clinical examination at the inclusion visit (non-sinus rhythm in ECG, body temperature > 38°C, blood pressure or heart rate outside the defined standards, etc.)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description "Intraosseous ultrasonography" Intraosseous ultrasonography at tibia before, during, and after a physiological vascular stimulation (venous occlusions, arterial occlusion, handgrip) All subjects of each sub-protocol receive identical intervention (single group assignment for each of 2 sub-protocols).
- Primary Outcome Measures
Name Time Method Change in tibial intracortical blood flow velocity, induced by physiological maneuvers in supine position (sub-protocol 1) before, at the end of venous occlusion (40 mmHg 3 minutes); before, at the end of arterial occlusion (200 mmHg 2 min); at 2, 5, and 10 min of post-occlusion period; before, at the end of handgrip (30% maximum voluntary force for 3 minutes) Velocity (mm/s) of intracortical blood flow at medial tibia level and its response to venous occlusion, arterial occlusion, handgrip, will be assessed via Ultrasound Vector Flow Mapping
- Secondary Outcome Measures
Name Time Method Change in leg skin and muscle blood flow, induced by physiological maneuvers in supine position (sub-protocol 1) before, at the end of venous occlusion (40 mmHg 3 minutes); before, at the end of arterial occlusion (200 mmHg 2 min); at 2, 5, and 10 min of post-occlusion period; before, at the end of handgrip (30% maximum voluntary force for 3 minutes) Leg skin blood flow (arbitrary units), leg muscle change in concentrations of oxy- and deoxy-hemoglobin (µmol/L), and their responses to venous occlusion, arterial occlusion, handgrip, will be assessed via Laser Doppler flowmetry and Near-Infrared Spectroscopy
Comparison of changes in tibial intracortical blood flow with changes in leg skin and muscle blood flow, induced by physiological maneuvers in supine position (sub-protocol 1) before, at the end of venous occlusion (40 mmHg 3 minutes); before, at the end of arterial occlusion (200 mmHg 2 min); at 2, 5, and 10 min of post-occlusion period; before, at the end of handgrip (30% maximum voluntary force for 3 minutes) Responses of leg intracortical, skin, and muscle blood flow to venous occlusion, arterial occlusion, and handgrip will be expressed as % baseline. Correlation of bone responses to skin and muscle responses (Pearson r) will be calculated.
Reproducibility of the change in tibial intracortical blood flow velocity, induced by physiological maneuvers in supine position (sub-protocol 1) before, at the end of venous occlusion (40 mmHg 3 minutes); before, at the end of arterial occlusion (200 mmHg 2 min); at 2, 5, and 10 min of post-occlusion period; before, at the end of handgrip (30% maximum voluntary force for 3 minutes) Measurements for sub-protocol 1 will be performed 2 times (visit 1 and visit 2 with 2-to-10-day interval), and Coefficient of variation in responses to physiological maneuvers (%) will be calculated
Change in tibial intracortical blood flow velocity, induced by occlusion maneuvers in +45° head up tilt position (sub-protocol 2) Ultrasonography acquisition sequences of 5 secondes will be performed before and during each occlusions. Velocity (mm/s) of intracortical blood flow at distal tibia level, and its responses to proximal cuff compression steps of 80 mmHg and 180 mmHg, will be assessed via Ultrasound Vector Flow Mapping.
Change in tibial ultradistal bone blood flow velocity, induced by occlusion maneuvers in +45° head up tilt position (sub-protocol 2) Ultrasonography acquisition sequences of 5 secondes will be performed before and during each occlusions. Velocity (mm/s) of intracortical blood flow at distal tibia level, and its responses to proximal cuff compression steps of 80 mmHg and 180 mmHg, will be assessed via Ultrasound Vector Flow Mapping.
Comparison of intraosseous ultrasonography and computed tomography for Cortical bone thickness characterisation (sub-protocol 2) First, intraosseous ultrasonography is performed at +45° head up tilt position (30 minutes for all occlusion steps), then the subject sits down and tomography is performed (10 minutes) Cortical thickness at distal tibia (mm) will be measured via peripheral quantitative computed tomography and via intraosseous ultrasonography. Correlation (Pearson r) between measurements will be calculated
Comparison of intraosseous ultrasonography and computed tomography for Cortical bone porosity characterisation (sub-protocol 2) First, intraosseous ultrasonography is performed at +45° head up tilt position (30 minutes for all occlusion steps), then the subject sits down and tomography is performed (10 minutes) Cortical density (mg/cm3) via peripheral quantitative computed tomography and cortical ultrasound propagation velocity (m/s) via intraosseous ultrasonography will be measured at distal tibia. Correlation (Pearson r) between measurements will be calculated.
Trial Locations
- Locations (2)
CHU d'Angers
🇫🇷Angers, France
CHU de Saint-Etienne
🇫🇷Saint-Étienne, France