Bone Perfusion Research Articles

Blood perfusion of patellar bone measured by dynamic contrast‐enhanced MRI in patients with patellofemoral pain: A case–control study

BackgroundAltered perfusion might play an important role in the pathophysiology of patellofemoral pain (PFP), a common knee complaint with unclear pathophysiology.PurposeTo investigate differences in dynamic contrast‐enhanced (DCE)‐MRI perfusion parameters between patients with PFP and healthy control subjects.Population/Subjects/Phantom/Specimen/Animal ModelThirty‐five adult patients with PFP and 44 healthy adult control subjects.Field Strength/Sequence3T DCE‐MRI consisting of a sagittal, anterior‐posterior, frequency‐encoded, fat‐suppressed 3D spoiled gradient‐echo sequence with intravenous contrast administration.AssessmentPatellar bone volumes of interest (VOIs) were delineated by a blinded observer. Quantitative perfusion parameters (kep and ktrans) were calculated from motion‐compensated DCE‐MRI data by fitting Tofts' model. Weighted mean and unweighted median values of kep and ktrans were computed within the patellar bone VOIs.Statistical TestsDifferences in patellar bone perfusion parameters were compared between groups by linear regression analyses, adjusted for confounders.ResultsMean differences of weighted mean and unweighted median were 0.0039 (95% confidence interval [CI] –0.0013; 0.0091) and 0.0052 (95% CI –0.0078; 0.018) for ktrans, and 0.046 (95% CI –0.021; 0.11) and 0.069 (95% CI –0.017; 0.15) for kep, respectively.All perfusion parameters were not significantly different between groups (P‐values: 0.32; 0.47 for ktrans, and 0.24; 0.15) for kep. However, a significant difference in variance between populations was observed for ktrans (P‐value 0.007).Data ConclusionHigher patellar bone perfusion parameters were found in patients with PFP when compared to healthy control subjects, but these differences were not statistically significant. This result, and the observed significant difference in ktrans variance, warrant further research. Level of Evidence: 1 Technical Efficacy: Stage 3J. Magn. Reson. Imaging 2018;47:1344–1350.

Skeletal vascular perfusion is altered in chronic kidney disease

Patients with chronic kidney disease (CKD) are at an alarming risk of cardiovascular disease and fracture-associated mortality. CKD has been shown to have negative effects on vascular reactivity and organ perfusion. Although alterations in bone blood flow are linked to dysregulation of bone remodeling and mass in multiple conditions, changes to skeletal perfusion in the setting of CKD have not been explored. The goal of this study was to establish the effect of CKD on skeletal perfusion in a rat model of CKD. In two experiments with endpoints at 30 and 35 weeks of age, respectively, normal (NL) and Cy/+ (CKD) animals (n = 6/group) underwent in vivo intra-cardiac fluorescent microsphere injection to assess bone tissue perfusion. These two separate time points aimed to describe skeletal perfusion at 30 and 35 weeks based on previous studies demonstrating significant progression of hyperparthyroid bone disease during this timeframe. CKD animals had blood urea nitrogen (BUN) levels significantly higher than NL at both 30 and 35 weeks. At 30 weeks, perfusion was significantly higher in the femoral cortex (+259%, p < 0.05) but not in the tibial cortex (+140%, p = 0.11) of CKD animals relative to NL littermates. Isolated tibial marrow perfusion at 30 weeks showed a trend toward being higher (+183%, p = 0.08) in CKD. At 35 weeks, perfusion was significantly higher in both the femoral cortex (+173%, p < 0.05) and the tibial cortex (+241%, p < 0.05) in CKD animals when compared to their normal littermates. Isolated tibial marrow perfusion (−57%, p <0.05) and vertebral body perfusion (−71%, p <0.05) were lower in CKD animals. The current study demonstrates two novel findings regarding bone perfusion in an animal model of high turnover CKD. First, cortical bone perfusion in CKD animals is higher than in normal animals. Second, alterations in bone marrow perfision differed among the stages of CKD and were distinct from perfusion to the cortical bone. Determining whether these changes in bone perfusion are drivers, propagators, or consequences of skeletal deterioration in CKD will necessitate further work.

Subchondral bone circulation in osteoarthritis of the human knee

The hypothesis of this study is that human subchondral bone exhibits abnormal patterns of perfusion in osteoarthritis (OA) that can be characterized by kinetic parameters of blood flow using dynamic contrast enhanced (DCE) MRI. Fifteen subjects with advanced OA of the knee and seven control subjects without OA were studied at 1.5T with DCE-MRI. Region of interest (ROIs) analysis of pharmacokinetic perfusion parameters were used to examine initial uptake and washout of the contrast agent in the lateral tibial plateau. Arterial and venous perfusion kinetics were abnormal in subchondral OA bone compared to those of normal controls. Time-intensity curves (TIC) exhibited delayed contrast clearance in OA knees compared to normal. Quantitatively, changes were observed in the kinetic parameters, kep, Akep, and kel. The mean kep and Akep were reduced in OA, compared to normal bone, indicating a reduction of arterial inflow and delayed signal enhancement. The kel in OA bone was lower than in normal bone, the negative kel indicating a reduction in venous outflow. The area under the TIC (AUC60) indicated greater residual contrast in OA bone. DCE-MRI can quantitatively assess subchondral bone perfusion kinetics in human OA and identify heterogeneous regions of perfusion deficits. The results are consistent with venous stasis in OA, reflecting venous outflow obstruction, and can affect intraosseous pressure, reduce arterial inflow, reduce oxygen content, and may contribute to altered cell signaling in, and the pathophysiology of, OA.

Assessment of the zonal variation of perfusion parameters in the femoral head: a 3-T dynamic contrast-enhanced MRI pilot study.

The objective was to describe MR perfusion characteristics of the femoral head, with a focus on the subchondral bone. This prospective monocentric study was approved by our local Ethics Committee. Written informed consent was obtained from all subjects. Dynamic contrast-enhanced MRI of the right hip was performed in 59 adults with suspected spondyloarthritis (32 women, 28 men). Mean age was 37.5 (±12.5) years. Regions of interest were drawn in the femoral head epiphysis, in the subchondral areas the most exposed to mechanical load (superolateral, anterosuperior, and posterior zones) and in areas less exposed to mechanical load (inferior subchondral zone and center of the femoral head). Semi-quantitative and pharmacokinetic parameters were calculated using the Tofts model. Statistical analysis was performed with a linear mixed model to compare the perfusion parameters in the different femoral head zones. Extravascular extracellular volume and area under the curve were lower in the superolateral zone than in the inferior zone (p=0.0135 and p<0.0001 respectively) and the central zone (p=0.007 and p=0.0134 respectively). Extravascular extracellular volume and rate constant were lower in the anterosuperior zone than in the inferior zones (p=0.011 and p=0.029). In the anterosuperior zone, extravascular extracellular volume was lower, and time to peak was higher than in the central zones (p=0.0056 and p=0.0013 respectively). No significant differences were found for any values between other paired zones. The perfusion of femoral head subchondral bone assessed with dynamic contrast-enhanced magnetic resonance imaging is not homogeneous: the areas exposed to more mechanical loading are less perfused.

Comparison of semi-quantitative and quantitative dynamic contrast-enhanced MRI evaluations of vertebral marrow perfusion in a rat osteoporosis model

BackgroundThis study aims to investigate the technical feasibility of semi-quantitative and quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in the assessment of longitudinal changes of marrow perfusion in a rat osteoporosis model, using bone mineral density (BMD) measured by micro-computed tomography (micro-CT) and histopathology as the gold standards.MethodsFifty rats were randomly assigned to the control group (n=25) and ovariectomy (OVX) group whose bilateral ovaries were excised (n=25). Semi-quantitative and quantitative DCE-MRI, micro-CT, and histopathological examinations were performed on lumbar vertebrae at baseline and 3, 6, 9, and 12 weeks after operation. The differences between the two groups in terms of semi-quantitative DCE-MRI parameter (maximum enhancement, Emax), quantitative DCE-MRI parameters (volume transfer constant, Ktrans; interstitial volume, Ve; and efflux rate constant, Kep), micro-CT parameter (BMD), and histopathological parameter (microvessel density, MVD) were compared at each of the time points using an independent-sample t test. The differences in these parameters between baseline and other time points in each group were assessed via Bonferroni’s multiple comparison test. A Pearson correlation analysis was applied to assess the relationships between DCE-MRI, micro-CT, and histopathological parameters.ResultsIn the OVX group, the Emax values decreased significantly compared with those of the control group at weeks 6 and 9 (p=0.003 and 0.004, respectively). The Ktrans values decreased significantly compared with those of the control group from week 3 (p<0.05). However, the Ve values decreased significantly only at week 9 (p=0.032), and no difference in the Kep was found between two groups. The BMD values of the OVX group decreased significantly compared with those of the control group from week 3 (p<0.05). Transmission electron microscopy showed tighter gaps between vascular endothelial cells with swollen mitochondria in the OVX group from week 3. The MVD values of the OVX group decreased significantly compared with those of the control group only at week 12 (p=0.023). A weak positive correlation of Emax and a strong positive correlation of Ktrans with MVD were found.ConclusionsCompared with semi-quantitative DCE-MRI, the quantitative DCE-MRI parameter Ktrans is a more sensitive and accurate index for detecting early reduced perfusion in osteoporotic bone.

Feasibility of Bone Perfusion Evaluation in Cadavers Using Indocyanine Green Fluorescence Angiography.

Bone perfusion evaluation methods in cadaver studies have yet to be established. The aim of this report was to introduce and validate the feasibility of indocyanine green (ICG) fluorescence angiography for evaluation of bone perfusion in the femoral medial condyle in cadavers. In 4 fresh nonembalmed cadavers (2 female), the descending genicular artery was dissected and carefully cannulated bilaterally. A 10 mL solution containing 5 mL ICG solution and 5 mL methylene blue solution was injected into the descending genicular artery. After the injection, the medial femoral condyle was cut with an oscillating saw. A photograph was taken of the cut ends of the bone. The cut ends of the bones were observed using a near-infrared camera. Images corresponding to the previously taken photographs of the cut ends were captured for comparative analysis. After injection of methylene blue and ICG, the blue dye could be seen in the periosteum in all specimens, but not inside the cortex or the cancellous region of the bone. When observed with ICG fluorescence angiography, however, the cancellous region was highlighted through small perforators penetrating the periosteum. Perfusion inside the medial femoral condyle in cadavers was confirmed using ICG fluorescence angiography. Our method can be especially beneficial in confirming the bone perfusion of a new bone flap based on a particular artery, both in cadavers as well as in patients, because ICG can be injected into specific arteries.

Focal osteonecrosis in the femoral head following stable anatomic fixation of displaced femoral neck fractures.

Femoral head (FH) osteonecrosis (ON) and subsequent segmental collapse is a major concern following displaced femoral neck fractures (FNF). We aimed to quantify residual perfusion to the FH following FNF and evaluate the viability of the FH overtime after surgical fixation. Twenty-three patients with FNF underwent dynamic contrast-enhanced (DCE)-MRI to estimate bone perfusion in the FH, using the contralateral side as control. Following open anatomic reduction and a length/angle-stable fixation, a special MRI sequence evaluated the FH for ON changes over time at 3 and 12months after surgery. We found significant compromise of both arterial inflow [83.1%-initial area under the curve (IAUC) and 73.8%-peak) and venous outflow (243.2%-elimination rate (K el)] in the FH of the fractured side. The supero-medial quadrant suffered the greatest decrease in arterial inflow with a significant decrease of 71.6% (IAUC) and 68.5% (peak). Post-operative MRI revealed a high rate (87%-20/23) of small ON segments within the FH, and all developed in the anterior aspect of the supero-medial quadrants. Fracture characteristics, including subcapital FNF, varus deformity, posterior roll-off ≥20° and Pauwel's angle of 30°-50° demonstrated a greater decrease in perfusion compared to contralateral controls. FNF significantly impaired the vascular supply to the FH, resulting in high incidence of small ON segments in the supero-medial quadrant of the FH. However, maintained perfusion, probably through the inferior retinacular system, coupled with urgent open anatomic reduction and stable fixation resulted in excellent clinical and radiographic outcomes despite a high rate of small ON segments noted on MRI. Level I: Prognostic Investigation.

Review of dynamic contrast-enhanced MRI: Technical aspects and applications in the musculoskeletal system.

5 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:875-890.

Dynamic contrast-enhanced MRI of the patellar bone: How to quantify perfusion.

PurposeTo identify the optimal combination of pharmacokinetic model and arterial input function (AIF) for quantitative analysis of blood perfusion in the patellar bone using dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI).Materials and MethodsThis method design study used a random subset of five control subjects from an Institutional Review Board (IRB)‐approved case–control study into patellofemoral pain, scanned on a 3T MR system with a contrast‐enhanced time‐resolved imaging of contrast kinetics (TRICKS) sequence. We systematically investigated the reproducibility of pharmacokinetic parameters for all combinations of Orton and Parker AIF models with Tofts, Extended Tofts (ETofts), and Brix pharmacokinetic models. Furthermore, we evaluated if the AIF should use literature parameters, be subject‐specific, or group‐specific. Model selection was based on the goodness‐of‐fit and the coefficient of variation of the pharmacokinetic parameters inside the patella. This extends previous studies that were not focused on the patella and did not evaluate as many combinations of arterial and pharmacokinetic models.ResultsThe vascular component in the ETofts model could not reliably be recovered (coefficient of variation [CV] of vp >50%) and the Brix model parameters showed high variability of up to 20% for kel across good AIF models. Compared to group‐specific AIF, the subject‐specific AIF's mostly had higher residual. The best reproducibility and goodness‐of‐fit were obtained by combining Tofts' pharmacokinetic model with the group‐specific Parker AIF.ConclusionWe identified several good combinations of pharmacokinetic models and AIF for quantitative analysis of perfusion in the patellar bone. The recommended combination is Tofts pharmacokinetic model combined with a group‐specific Parker AIF model. Level of Evidence: 2 Technical Efficacy: Stage 1J. Magn. Reson. Imaging 2018;47:848–858.

Bone microvascular flow differs from skin microvascular flow in response to head-down tilt.

Loss of hydrostatic pressures in microgravity may alter skin and bone microvascular flows in the lower extremities and potentially reduce wound healing and bone fracture repair. The purpose of this study was to determine the rate at which skin and bone microvascular flows respond to head-down tilt (HDT). We hypothesized that microvascular flows in tibial bone and overlying skin would increase at different rates during HDT. Tibial bone and skin microvascular flows were measured simultaneously using photoplethysmography (PPG) in a total of 17 subjects during sitting (control posture), supine, 6° HDT, 15° HDT, and 30° HDT postures in random order. With greater angles of HDT, bone microvascular flow increased significantly, but skin microvascular flow did not change. Tibial bone microvascular flow increased from the sitting control posture (0.77 ± 0.41 V) to supine (1.95 ± 1.01 V, P = 0.001) and from supine posture to 15° HDT (3.74 ± 2.43 V, P = 0.004) and 30° HDT (3.91 ± 2.68 V, P = 0.006). Skin microvascular flow increased from sitting (0.703 ± 0.75 V) to supine (2.19 ± 1.72 V, P = 0.02) but did not change from supine posture to HDT (P = 1.0). We show for the first time that microcirculatory flows in skin and bone of the leg respond to simulated microgravity at different rates. These altered levels of blood perfusion may affect rates of wound and bone fracture healing in spaceflight.NEW & NOTEWORTHY Our data show that bone microvascular flow increases more than cutaneous blood flow with greater degrees of head-down tilt. A higher level of perfusion in bone may give insight into the bone mineral density loss in lower extremities of astronauts and why similar tissue degradation is not observed in the skin of the same areas.

Knee subchondral bone perfusion and its relationship to marrow fat and trabeculation on multi-parametric MRI and micro-CT in experimental CKD

The pathogenesis of chronic kidney disease (CKD) is multifactorial. In the progression of CKD arthropathy, arteriosclerosis may alter the knee subchondral bone marrow by altering blood flow through the bone vasculature. Herein, multi-parametric MRI assessment, including dynamic contrast enhanced magnetic resonance imaging (DCE-MRI), magnetic resonance spectroscopy (MRS), MRI T2*, contrast enhanced MR angiography (CE-MRA), and micro-CT were applied in a rodent nephrectomy model to: 1) investigate the blood perfusion of subchondral bone marrow and its relationship to fat water content and trabeculation pattern in CKD and 2) demonstrate the feasibility of using multi-parametric MRI parameters as imaging biomarkers to evaluate the disease’s progression. Two groups of rats in our study underwent either 1) no intervention or 2) 5/6 nephrectomy. We found that in the CKD group, perfusion amplitude A and elimination constant kel values were significantly decreased, and vascular permeability kep was significantly increased. MRS showed that fat fraction (FF) was significantly lower, water fraction (WF) was significantly higher in the CKD group. Micro-CT showed a significant loss of trabecular bone. Knee subchondral bone marrow perfusion deficiency in experimental CKD may be associated with decreased fat content, increased water content, and sparse trabeculation.

Anatomic study of the vascular perfusion of the sternum and its clinical relevance in deep sternal wound infection.

Introduction: Deep sternal wound infections (DSWI) are a rare but devastating complication after median sternotomy. Minor perfusion in bone and soft tissue, especially after recruiting the internal mammary artery for bypass supports the development of wound infection and nonunion of the sternal bone. The aim of the study was the macroscopic and radiological presentation of the vascular system supplying the sternum, in particular the compensating blood supply routes in the event that the internal mammary artery is no longer available after use as a bypass vessel.Method: This anatomic study was carried out on the anterior chest wall of 7 specimens. The thorax plates of 7 specimens were analyzed macroscopically after microsurgical preparation. Different anatomic preparations were produced using different contrast or form-giving substances. Radiological analysis and three-dimensional reconstructions were performed to show alternative, collateral sternal vessel perfusion under estimation of the loss of the internal thoracic artery due to a bypass.Results: The length of the ITA (internal thoracic artery), measured from the beginning of the first rib to the division into the superior epigastric artery and musculophrenic artery, was an average of 16.3 cm. On average, 18.5 branches were delivered from each artery, 10 medially to the sternum supply, and 8 to the intercostal muscle. Conclusion: Our analysis gives an overview of the macroanatomic vessel system supplying the sternal bone, describing especially a common trunk deriving from the ITA and supplying multiple branches and playing an important role in building a collateral circulation of the sternum.For better evaluation, in vivo CT analysis with contrast media should be performed in patients prior to the operation and directly after the use of the double ITA to demonstrate the change in perfusion of the sternum.In the future, preconditioning of the sternum by coiling the deriving branches could become an option, although patient selection has to be improved and further analysis of the topic performed.

Quantitative MRI and spectroscopy of bone marrow.

Bone marrow is one of the largest organs in the human body, enclosing adipocytes, hematopoietic stem cells, which are responsible for blood cell production, and mesenchymal stem cells, which are responsible for the production of adipocytes and bone cells. Magnetic resonance imaging (MRI) is the ideal imaging modality to monitor bone marrow changes in healthy and pathological states, thanks to its inherent rich soft‐tissue contrast. Quantitative bone marrow MRI and magnetic resonance spectroscopy (MRS) techniques have been also developed in order to quantify changes in bone marrow water–fat composition, cellularity and perfusion in different pathologies, and to assist in understanding the role of bone marrow in the pathophysiology of systemic diseases (e.g. osteoporosis). The present review summarizes a large selection of studies published until March 2017 in proton‐based quantitative MRI and MRS of bone marrow. Some basic knowledge about bone marrow anatomy and physiology is first reviewed. The most important technical aspects of quantitative MR methods measuring bone marrow water–fat composition, fatty acid composition, perfusion, and diffusion are then described. Finally, previous MR studies are reviewed on the application of quantitative MR techniques in both healthy aging and diseased bone marrow affected by osteoporosis, fractures, metabolic diseases, multiple myeloma, and bone metastases. Level of Evidence: 3 Technical Efficacy: Stage 2J. Magn. Reson. Imaging 2018;47:332–353.

Assessment of regional bone tissue perfusion in rats using fluorescent microspheres

Disturbances in bone blood flow have been shown to have deleterious effects on bone properties yet there remain many unanswered questions about skeletal perfusion in health and disease, partially due to the complexity of measurement methodologies. The goal of this study was use fluorescent microspheres in rats to assess regional bone perfusion by adapting mouse-specific fluorescent microsphere protocol. Ten fifteen-week old Sprague Dawley rats were injected with fluorescent microspheres either via cardiac injection (n=5) or via tail vein injection (n=5). Femora and tibiae were harvested and processed to determine tissue fluorescence density (TFD) which is proportional to the number of spheres trapped in the tissue capillaries. Right and left total femoral TFD (2.77±0.38 and 2.70±0.24, respectively) and right and left tibial TFD (1.11±0.26 and 1.08±0.34, respectively) displayed bilateral symmetry in flow when assessed in cardiac injected animals. Partitioning of the bone perfusion into three segments along the length of the bone showed the distal femur and proximal tibia received the greatest amount of perfusion within their respective bones. Tail vein injection resulted in unacceptably low TFD levels in the tibia from 4 of the 5 animals. In conclusion this report demonstrates the viability of cardiac injection of fluorescent microspheres to assess bone tissue perfusion in rats.

Age-Related Changes in the Bone Marrow

To summarize current knowledge with regards to age-related changes in the bone marrow from childhood to senility and discuss how these changes are affected in patients with osteoporosis. There is a dramatic increase in marrow fat content in females around the time of the menopause in line with a reduction in bone mass. Marrow fat content is very responsive to physiological changes in estrogen and increase in marrow fat can be reversed by estrogen replacement. Marrow fat composition, rather than content, seems to be related to insufficiency fracture and diabetes. MR imaging is a very good way of non-invasively studying marrow fat changes throughout life—both content and composition. Marrow fat content is an inverse marker of red marrow content. Red marrow content drives bone perfusion. Bone perfusion affects marrow nutrition and bone healing. Research into the fascinating bone-fat-perfusion relationship has only just began.

Is Diabetic Skeletal Fragility Associated with Microvascular Complications in Bone?

The objective of this literature review is to determine whether there are indications that microvascular complications occur in diabetic bone. Evidence definitively linking diabetic skeletal fragility with microvascular complications in bone remains elusive. Circumstantial evidence, some recent and some lost to time, suggests that atherosclerotic vascular diseases such as peripheral arterial disease cause poor blood perfusion of bone and subsequent hypoxia and contribute to low bone density and high cortical porosity, patterns similar to some recently observed in diabetic subjects. Evidence also exists to suggest that potentially anti-angiogenic conditions, such as impaired vascular endothelial growth factor (VEGF) signaling, predominate in diabetic bone. Microvascular complications may contribute, in part, to diabetic skeletal fragility but data supporting this interpretation are primarily circumstantial at this time. This review highlights gaps in our knowledge and hopefully spurs further discussions and research on this topic.

Intravoxel incoherent motion (IVIM) analysis of vertebral bone marrow changes after radiation exposure from diagnostic imaging and interventional procedures.

Background High cumulative radiation dose in cancer patients warrants systemic examination of possible changes in bone marrow. Purpose To assess retrospectively changes in vertebral bone marrow diffusion and perfusion using intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) in hepatocellular carcinoma (HCC) patients after exposure to radiation from diagnostic imaging and interventional procedures. Material and Methods A total of 21 IVIM-DWI sets in 20 HCC patients, consisting of baseline and follow-up liver magnetic resonance imaging (MRI) with an interval less than 100 days, were reviewed after varying levels of radiation exposure from transarterial chemoembolization (TACE), multiphase liver CT, and abdominal radiography. IVIM parameters (apparent diffusion coefficient [ADC], true diffusion coefficient [D], pseudodiffusion coefficient [D*], and perfusion fraction [PF]) of vertebral bone marrow were analyzed for significant differences between baseline and follow-up MRI using Wilcoxon signed-rank test, and for correlations with cumulative effective dose, as well as time interval between last radiation exposure and follow-up MRI using Spearman's correlation. Results Compared to baseline MRI, ADC, D*, and PF significantly decreased on follow-up MRI (ADC: median [interquartile range], 0.405 × 103 mm2/s [0.364-0.477] versus 0.390 [0.348-0.461]; D*: 24.011 [18.141-29.584] versus 20.815 [15.022-28.347]; PF: 10.960% [8.828-12.985] versus 9.125 [8.606-12.803]) ( P < 0.05). There was no significant difference in D ( P = 0.807). Cumulative effective dose was moderately correlated with decrease in D* (r = 0.434). In addition, longer intervals between last exposure and follow-up MRI showed negative correlations with changes in D and ADC (r = -0.352 and -0.333, respectively). Conclusion Vertebral bone marrow diffusion and perfusion parameters were significantly changed after exposure to medical radiation.

Femoral bone perfusion through the nutrient foramen during growth and locomotor development of western grey kangaroos (Macropus fuliginosus).

The nutrient artery passes through the nutrient foramen on the shaft of the femur and supplies more than half of the total blood flow to the bone. Assuming that the size of the nutrient foramen correlates with the size of the nutrient artery, an index of blood flow rate (Qi) can be calculated from nutrient foramen dimensions. Interspecific Qi is proportional to locomotor activity levels in adult mammals, birds and reptiles. However, no studies have yet estimated intraspecific Qi to test for the effects of growth and locomotor development on bone blood flow requirements. In this study, we used micro-CT and medical CT scanning to measure femoral dimensions and foramen radius to calculate femoral Qi during the in-pouch and post-pouch life stages of western grey kangaroos (Macropus fuliginosus) weighing 5.7 g to 70.5 kg and representing a 12,350-fold range in body mass. A biphasic scaling relationship between Qi and body mass was observed (breakpoint at ca. 1-5 kg body mass right before permanent pouch exit), with a steep exponent of 0.96±0.09 (95% CI) during the in-pouch life stage and a statistically independent exponent of -0.59±0.90 during the post-pouch life stage. In-pouch joeys showed Qi values that were 50-100 times higher than those of adult diprotodont marsupials of the same body mass, but gradually converged with them as post-pouch adults. Bone modelling during growth appears to be the main determinant of femoral bone blood flow during in-pouch development, whereas bone remodelling for micro-fracture repair due to locomotion gradually becomes the main determinant when kangaroos leave the pouch and become more active.

Cartilage MRI T2∗ relaxation time and perfusion changes of the knee in a 5/6 nephrectomy rat model of chronic kidney disease.

Chronic kidney disease (CKD) is characterized by metabolic disturbances in calcium and phosphorus homeostasis as kidney function declines. Alterations in blood perfusion in bone resulting from arteriosclerosis of bone vessels may relate to the progression of CKD. Herein, change in dynamic contrast enhanced (DCE) MRI parameters (A: amplitude, kel: elimination constant, and kep: permeability rate constant) and MRI T2∗ relaxation time of the knee cartilage were measured in a rodent nephrectomy model in order to (1) examine the relationship of peripheral blood perfusion to CKD and (2) demonstrate the feasibility of using DCE-MRI parameters and MRI T2∗ as imaging biomarkers to monitor disease progression. Two groups of male Sprague-Dawley rats received either (1) no intervention or (2) 5/6 nephrectomy. We found that the CKD group (compared with the control group) had lower A and kel values and similar kep value in the lateral and medial articular cartilages beginning at 12 weeks (P<0.05); statistically significantly higher T2∗ values in the lateral and medial articular cartilages beginning at 18 weeks (P<0.05); statistically significantly decreased inner luminal diameter of the popliteal artery, and altered structure of the lateral and medial articular cartilages (P<0.05). Perfusion deficiency and CKD may be related. DCE parameters and MRI T2∗ could serve as imaging biomarkers of cartilage degeneration in CKD progression.

Naringin promotes fracture healing through stimulation of angiogenesis by regulating the VEGF/VEGFR-2 signaling pathway in osteoporotic rats

Postmenopausal osteoporosis is characterized by a reduction in the number of sinusoidal and arterial capillaries in the bone marrow and reduced bone perfusion. Thus, osteogenesis and angiogenesis are coupled in the process of osteoporosis formation and fracture healing. Naringin is the main ingredient of the root Rhizoma Drynariae, a traditional Chinese medicine, and it has potential effects on promoting fracture healing. However, whether naringin stimulates angiogenesis in the process of bone healing is unclear. Here, we show that naringin promotes fracture healing through stimulating angiogenesis by regulating the VEGF/VEGFR-2 signaling pathway in osteoporotic rats.