Intraosseous Doppler Ultrasonography to Study Skeletal Physiology: Exploratory Study Before Use in Space Physiology

N/ACompletedNCT06206031

University Hospital, Angers30 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

BASIC_SCIENCE

Masking

Interventions

Intraosseous ultrasonography at tibia before, during, and after a physiological vascular stimulation (venous occlusions, arterial occlusion, handgrip)DEVICE

Timing for sub-protocol 1 (performed twice with 2-to-10-day interval): donning in supine position - rest 5 minutes - venous occlusion to 40 mmHg 3 minutes - rest 10 minutes - arterial occlusion to 200mmHg 2 minutes - post-occlusion period 10 minutes - rest 10 minutes - static handgrip 30% Maximum Voluntary Force 3 minutes - recovery 2 minutes and doffing. Timing for sub-protocol 2 (performed once). First, two sequences of intraosseous ultrasonography are performed in 45° head-up tilt position, with 10-minutes rest between sequences: donning and rest 5 minutes - occlusion to 80 mmHg 2 minutes - rest 10 minutes - occlusion to 180 mmHg 2 minutes - rest 10 minutes. During the first sequence, ultrasonography probe is positioned between middle and lower third of tibia for cortical bone measurement; during the second - at distal epiphysis of the tibia for trabecular bone measurement. After ultrasonography, subject is sitting down for 10 minutes for computed tomography.

Eligibility

Sex: MALEMin age: 20 YearsMax age: 70 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria for sub-protocol 1: * Male aged 20-40 years Inclusion criteria for sub-protocol 2: * Male aged 20-40 years \& 50-70 years * Body height of at least 180 cm (in order to have tibia length of 43-45 cm allowing the positioning of ultrasonic probe at distal tibia, and occlusive cuff at calf level) * Bone densitometry with available report performed within 5 last years (if none has been done, possibility to perform densitometry covered by the study at selection or inclusion visit) Inclusion criteria common for both sub-protocols: * Healthy volunteer without chronic pathology (in particular no known rhythm disorder) or long-term treatment * No symptomatic acute medical event requiring treatment on the visit days * No history of tibia fractures * Body Mass Index between 19 and 26 * Affiliation to the French Social Security System * Written informed consent Non-Inclusion criteria: * Inability to stay still for 20 minutes (tremor) * Active smoking (stopped less than 1 year ago) * History of prolonged corticosteroid treatment * Deprivation of liberty by legal or administrative decision * Subject to involuntary psychiatric treatment * Subject to a legal protection measure * For sub-study 1: Osteoporosis known at interview Exclusion Criteria: * 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.)

Outcomes

Primary Outcomes

Change in tibial intracortical blood flow velocity, induced by physiological maneuvers in supine position (sub-protocol 1)

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

Time frame: 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)

Secondary Outcomes

Change in leg skin and muscle blood flow, induced by physiological maneuvers in supine position (sub-protocol 1)

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)

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)

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)

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.

Time frame: Ultrasonography acquisition sequences of 5 secondes will be performed before and during each occlusions.

Change in tibial ultradistal bone blood flow velocity, induced by occlusion maneuvers in +45° head up tilt position (sub-protocol 2)

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.

Time frame: Ultrasonography acquisition sequences of 5 secondes will be performed before and during each occlusions.

Comparison of intraosseous ultrasonography and computed tomography for Cortical bone thickness characterisation (sub-protocol 2)

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

Time frame: 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)

Comparison of intraosseous ultrasonography and computed tomography for Cortical bone porosity characterisation (sub-protocol 2)

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.