Erick O. Buko

1. Despite government efforts to reduce social disparities, many children become street-connected in Namibia and across Afrika, a spelling used here to emphasise locally grounded social work approa...

Purpose: Intravoxel incoherent motion (IVIM) diffusion‐weighted imaging of tissue perfusion and diffusion has limited signal in low‐perfused tissues, which poses a challenge in measuring IVIM parameters. This work proposes an optimized analytical segmented (opAS) method for extracting IVIM parameters and compares its performance with prior segmented (S), oversegmented (OS), and analytical segmented (AS) fitting methods.Methods: The four fitting methods were compared using numerical simulations and retrospective analysis of IVIM data of a piglet model of bone marrow ischemia. The simulations compared the accuracy and precision of the four methods for different combinations of IVIM perfusion‐related parameters (D*, pseudo‐diffusion coefficient; and f, pseudo‐diffusion fraction) at a fixed molecular‐diffusion coefficient (D). In vivo data from n = 11 piglets were analyzed using the four methods to compare their sensitivities in detecting lack of perfusion in ischemic versus perfused pairs of femoral heads.Results: In simulation, opAS had the lowest errors in estimating D, f, D*, and f × D* across all signal‐to‐noise ratio (SNR) levels, particularly in challenging parameter combinations of low f and D*. In the piglet model, all four IVIM fitting methods consistently found that D increased and f and f × D* decreased in the ischemic versus perfused femoral heads. However, D* was only consistently decreased in the ischemic versus perfused femoral heads using the AS and opAS methods.Conclusion: The opAS method more accurately estimates IVIM parameters than the S, OS, and AS approaches, particularly perfusion‐related parameters (D* and f) in low‐perfused tissues.

Clinical management of children with Legg-Calvé-Perthes Disease (LCPD) is hampered by incomplete understanding of how the extent of ischemic injury and the duration and quality of subsequent repair determine patient outcome. The traditional piglet model of LCPD is limited to capturing global femoral head ischemia; thus, a new model is needed in which the extent of ischemia can be varied to replicate the spectrum of disease seen in children. In this exploratory study, we used an iterative approach to test and refine methods to bilaterally occlude vessels supplying the femoral heads in n = 8 young piglets under angiographic control. The deep and/or acetabular medial femoral circumflex arteries (DMFCA and AMFCA) were identified and embolized using either embolic particles or liquid embolic agents. The extent of ischemia was assessed immediately post-embolization (4 piglets) and/or 7 days following embolization (7 piglets) using contrast-enhanced magnetic resonance imaging (CE-MRI). After the final CE-MRI, piglets were euthanized, and their femora were harvested for histologic evaluation. Embolization of the DMFCA alone caused transient ischemia that largely resolved by 7 days with small regions of fibrovascular repair of ischemic injury remaining on histology. Embolization of both the DMFCA and AMFCA resulted in a greater degree of pathologic changes at 7 days post-operatively, but also with nearly complete restoration of femoral head perfusion. We found that combining injection of embolic particles with subsequent placement of an embolic micro-coil was the most effective approach to induce ischemic injury, which may be aided in larger piglets. While our findings should be interpreted cautiously due to the wide range in the age and size of animals investigated, they demonstrate that transarterial embolization of the vascular supply of the femoral head results in transient ischemia and histological changes consistent with partial ischemic injury. These results will inform further development of a minimally invasive piglet model of LCPD that offers a unique representation of the spectrum of pathophysiology of LCPD compared to the traditional model.

Legg‐Calvé‐Perthes disease (LCPD) is a childhood hip disorder characterized by ischemic injury to the epiphysis of the femoral head, but changes to the metaphysis have also been implicated in its pathogenesis. Quantitative magnetic resonance imaging (MRI) relaxation time mapping techniques are potentially useful to detect injury in LCPD, but studies to date have focused on the epiphysis. The purpose of this study was to assess whether T2, T1ρ, adiabatic T1ρ, and adiabatic T2ρ relaxation times can detect early metaphyseal changes in an LCPD piglet model. Complete epiphyseal ischemia of one femoral head was surgically induced and confirmed using contrast‐enhanced MRI in n = 10 6‐week‐old piglets; the contralateral side was unoperated. The bilateral hips were imaged 1 week after surgery in vivo at 3T MRI using relaxation time mapping and contrast‐enhanced MRI. Relaxation times and thicknesses of the metaphyseal primary and secondary spongiosa were measured and compared between the ischemic and contralateral‐control femoral heads using paired t‐tests. In the ischemic femoral heads, T2 relaxation times were significantly increased in the primary spongiosa (6.7 ± 9.8 ms, p = 0.029), and T2, T1ρ, adiabatic T1ρ, and adiabatic T2ρ relaxation times were significantly decreased in the secondary spongiosa (respectively: −13.3 ± 9.3 ms, p = 0.013; −32 ± 23 ms, p < 0.001; −43 ± 41 ms, p = 0.009; and −39 ± 13 ms, p < 0.001). The secondary spongiosa thickness was also significantly decreased in the ischemic femoral heads (p < 0.001). In conclusion, T2, T1ρ, adiabatic T1ρ, and adiabatic T2ρ relaxation time mapping techniques can detect early changes in the metaphysis following ischemic injury to the epiphysis of the femoral head in a piglet model of LCPD.

Failure of endochondral ossification due to interruption of the vascular supply to the epiphyseal cartilage is a critical step in the development of osteochondritis dissecans (OCD). Herein we describe the vascular architecture of the distal humeral epiphyseal cartilage in pigs and identify characteristic features that have been associated with sites predisposed to OCD development across species. Distal humeral specimens were harvested from pigs (n = 5, ages = 1, 10, 18, 30, and, 42 days old) and imaged at 9.4T magnetic resonance imaging (MRI) using a 3D gradient recalled echo sequence. The MRI data were processed using a quantitative susceptibility mapping (QSM) pipeline to visualize the vascular architecture. Specimens were also evaluated histologically to identify the presence of ischemic epiphyseal cartilage necrosis (osteochondrosis [OC]‐latens) and associated failure of endochondral ossification (OC‐manifesta). The QSM data enabled visualization of two distinct vascular beds arising from the perichondrium at the lateral and medial aspects of the distal humeral epiphysis. Elongated vessels originating from these beds coursed axially to supply the lateral and medial thirds of epiphyseal cartilage. At 18 days of age and older, a shift from perichondrial to transosseous blood supply was noted axially, which appeared more pronounced on the lateral side. This shift coincided with histologic identification of OC‐latens (30‐ and 42‐day‐old specimens) and OC‐manifesta (18‐ and 42‐day‐old specimens) lesions in the corresponding regions. The vascular anatomy and its evolution at the distal humeral epiphysis closely resembles that previously reported at predilection sites of knee OCD, suggesting a shared pathophysiology between the knee and elbow joints.

The intervertebral disc (IVD) aids in motion and acts to absorb energy transmitted to the spine. With little inherent regenerative capacity, degeneration of the intervertebral disc results in intervertebral disc disease, which contributes to low back pain and significant disability in many individuals. Increasing evidence suggests that IVD degeneration is a disease of the whole joint that is associated with significant inflammation. Moreover, studies show elevated macrophage accumulation within the IVD with increasing levels of disease severity; however, we still need to understand the roles, be they causative or consequential, of macrophages during the degenerative process. In this narrative review, we discuss hallmarks of IVD degeneration, showcase evidence of macrophage involvement during disc degeneration, and explore burgeoning research aimed at understanding the molecular pathways regulating macrophage functions during intervertebral disc degeneration.

The proposed dual-echo phase-contrast MRI method can be used to rapidly encode myocardial and transmitral blood flow velocities with sufficient velocity sensitivity within one repetition time to pe... PurposeTo develop a dual-echo phase-contrast (DEPC) MRI approach with which each echo is acquired by using a different velocity sensitivity within one repetition time (TR) and demonstrate the feasi...