MRI-BASED GRAFT MATURITY AFTER BLOOD FLOW RESTRICTION TRAINING IN BONE-PATELLAR TENDON-BONE ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION:
A RANDOMIZED CONTROLLED STUDY

The bone-patellar tendon-bone (BPTB) and hamstring tendon autograft are
commonly used in anterior cruciate ligament (ACL) reconstruction [1]. Although,
the BPTB has superior stability compared to the hamstring tendon autograft,
some studies have found that it has more donor-site morbidity [2, 3]. After ACL
reconstruction, the autograft changes from a tendinous to a ligamentous
intra-articular appearance also known as graft maturation [4]. Previous studies
have demonstrated three characteristic stages of graft maturation: an early
healing phase, followed by a phase of proliferation and finally a phase of
ligamentization [4]. During these phases of graft maturation, changes in
cellularity, vascularity and extracellular matrix transform characteristics
into properties of an intact ACL [5].
Range of motion, knee stability, patient-reported outcome measurements (PROMs),
muscle strength and patient satisfaction have traditionally been used to
evaluate the success of ACL reconstruction and timing of safe return to
pre-injury level of sport [6]. However, these outcome measurements lack the
sensitivity to determine graft maturity [7]. Graft maturity assessed as graft
signal intensity (signal-to-noise quotient, SNQ) on magnetic resonance imaging
(MRI) is correlated with strength and biomechanical properties of the
reconstructed ACL [8]. Therefore, graft maturity may better assess timing of
safe return to pre-injury level of sport.
In ACL reconstruction rehabilitation, there are concerns that the gold standard
heavy-load resistance training (HLRT) may have detrimental effects on ACL graft
maturation [9]. Therefore, low-load blood flow restriction training (LL-BFRT)
has been suggested as an alternative to HLRT [9]. As LL-BFRT is an increasingly
popular method for the rehabilitation after an ACL reconstruction, it is
important to evaluate the value of this treatment [11]. Previous studies showed
promising results of LL-BFRT on muscle strength in healthy participants [10].
The main objective of this study is to evaluate the effect of LL-BFRT on
MRI-based graft maturity after BPTB ACL reconstruction compared to HLRT. The
secondary objectives are to investigate the effect of LL-BFRT on donor-site
morbidity, range of motion, knee stability, PROMs, muscle strength and safe
return to pre-injury level of sport. Furthermore, feasibility and safety of
rehabilitation will be assessed.

Primary objective: The effect of LL-BFRT on MRI-based graft maturity after BPTB
ACL reconstruction compared to HLRT.
Secondary objectives: The effect of LL-BFRT on donor-site morbidity, range of
motion, knee stability, PROMs, muscle strength, safe return to pre-injury level
of sport and patient satisfaction compared to HLRT. Furthermore, feasibility
and safety of rehabilitation (LL-BFRT or HLRT) will be assessed.

A randomized controlled study. This study will be conducted in the Netherlands
and aims for completion within 48 months.

Patients in the LL-BFRT group will perform four sets (30, 15, 15 and 15
repetitions, respectively) of unilateral leg press, seated leg extension,
deadlift and squat exercises with 30s inter-set rest periods throughout a 0-90°
range of motion at 30% one-repetition maximum [9, 15]. BFR will be achieved
using an automatic personalized tourniquet system (PTS) (MAD-UP, Angers,
France) designed to automatically calculate limb occlusion pressure (Figure 1).
Limb occlusion pressure is defined as the minimum pressure required for blood
flow occlusion, with clinically acceptable accuracy and high reliability. Limb
occlusion pressure will be calculated in the position the exercise will be
performed. BFR is comprised of a dual-purpose easy-fit variable contour nylon
cuff (11.5x86 cm, 5mm thick) connected by airtight hose tubing and
automatically regulates pressure within acceptable limits. A limb occlusion
pressure of 80% with BFR will be applied during each exercise with 60s
deflation between different exercises.

5.2 Comparison
Patients in the HLRT group will perform 3x10 reps (30s inter-set rest) of
unilateral leg press, seated leg extension, deadlift and squat exercises
exercise throughout a 0-90° range of motion with incremental increase in
external-load up to 70% of patients* one-repetition maximum [15].

LL-BFRT promotes muscle hypertrophy and strength. In addition, LL-BFRT can
reduce pain and effusion which results in improved physical function. LL-BFRT
has been suggested to increase the risk of adverse cardiovascular or
cerebrovascular events in diseases such as severe hypertension and sickle cell
anemia. Therefore, patients at risk of adverse reactions of BFR application
will be excluded. No other side-effects of BFR training have been reported.