Harpal Gahunia - Academia.edu (original) (raw)

Papers by Harpal Gahunia

Orthopedic Clinics of North America, Apr 1, 2012

Springer eBooks, 2020

Cartilage is a dynamic tissue with enhanced complexity attributed to the existence of numerous de... more Cartilage is a dynamic tissue with enhanced complexity attributed to the existence of numerous developmental phases and overlap in phenotypic gene expression with related cell types. This chapter reviews the recent advances in molecular biology that illuminate the factors that drive and control articular cartilage growth and development. The objective is to provide a better understanding of the key molecular and genetic participants during the growth and development of articular-epiphyseal cartilage (AEC) and the epiphyseal growth plate (GP).

Articular cartilage serves as a lubricated, wear-resistant, friction-reducing self-maintaining ma... more Articular cartilage serves as a lubricated, wear-resistant, friction-reducing self-maintaining material that is slightly compressible to evenly distribute forces onto the bone. Articular cartilage macromolecular composition and architecture and its biomechanical properties are well adapted to withstand mechanical loads increasingly for a ten-decade lifetime. The three-dimensional orientation of the structural molecules and various levels of compartmentalization, namely, the horizontal zones from the articular surface to the underlying subchondral bone as well as interstitially from the surface of the chondrocytes, enable articular cartilage function by facilitating smooth knee movements by reducing friction and absorbing the impact of loading. Coupled with the biomechanical function of articular cartilage in its entirety, articular cartilage lubrication mechanisms provide almost frictionless surfaces between moving joints and do this throughout life adapting to both age and arthritic disease.

Osteoarthritis and Cartilage, Apr 1, 2016

Springer eBooks, 2020

Aging implies changes in articular cartilage cells and the surrounding extracellular matrix (ECM)... more Aging implies changes in articular cartilage cells and the surrounding extracellular matrix (ECM) that are reflective of metabolic changes related to time alone. For chondrocytes, these are genomic and intracytoplasmic changes that lessen their capacity to respond and control their extracellular environment; for the matrix, these are changes that lead to decreased hydration and increased brittleness of the tissue. Clinically, this can manifest as decreased capacity to withstand mechanical forces leading to degenerative arthritis.

Osteoarthritis and Cartilage, 2006

Objective: This study was performed to non-invasively visualize and characterize osteochondral (O... more Objective: This study was performed to non-invasively visualize and characterize osteochondral (OC) repair in ex vivo goat stifles using an 8 T magnetic resonance imaging (MRI) scanner and to compare the MR morphology with images obtained from 1.5 T, gross morphology and histology. Methods: Mature, neutered male goats were assigned to an 8-week (n Z 4) or 16-week (n Z 4) study period. Two cylindrical OC defects (7 mm diameter, full cartilage thickness and 1 mm into subchondral bone) were surgically created in the right stifle: one in the medial femoral condyle (MFC) and the other in the trochlear groove (TG). The implant matrices (non-woven or foam) were secured in the defect using a bottom anchored fixation device (FD). The contralateral left stifles served as time zero controls. At the day of necropsy, implants were placed at both defect sites (MFC and TG) on the normal left stifles. Following necropsy, the ex vivo goat stifles (intact and encapsulated) were disarticulated. Within 24 h postnecropsy, MR scans of the stifles along the mid-sagittal plane of the OC defect were acquired at 8 T and 1.5 T. MR relaxation times, T1 and T2, were measured at the region of repair tissue (RT) and adjacent native cartilage. Immediately after MR imaging, the stifles were dissected, grossly examined, and a sagittal OC block corresponding to the MR region of interest was prepared for formalin fixation. Results: The high-resolution MR images enabled visualization of cartilage and bone integrity surrounding the implant as well as delineating the margins of RT/implant matrix and the FD. On spin echo sequence, the RT variably appeared as high, intermediate or low MR signal intensity; whereas, the FD always appeared as low signal intensity. In general, the MR signal intensity of 8-week RT was slightly higher compared to 16week RT; however, there was no difference in RT morphology of stifles implanted with the non-woven matrix or foam matrix. Subchondral sclerosis appeared as low signal intensity. The 8 T MR images showed better delineation of the stifle tissues compared to the images acquired at 1.5 T. The T2 relaxation time of the RT appears to indicate (inconclusive due to small number of samples) a slight variation in the RT type between 8 weeks and 16 weeks. At both study times, the defects grossly appeared whitish to reddish but did not have the characteristic hyaline appearance typical of articular cartilage (AC). The gross appearance of the MFC and TG RT differed, which was predominantly mottled and recessed with fissuring of adjacent native AC in the MFC. Histologically, the RT of both 8-week and 16-week postsurgical defects predominantly comprised fibrovascular connective tissue with only few samples showing the presence of fibrocartilaginous and/or hypertrophic chondrocytes within the defect RT at 8 weeks. Also, compared to 8-week, the 16-week RT appeared to be more fibrotic. Conclusion: Using 8 T scanner, high-resolution MR images of ex vivo encapsulated goat stifles confirmed the capability of high-field MR imaging to distinguish the defect RT from the FD and adjacent joint tissues. The extent of OC repair and adjacent bone lesions (at 8 weeks and 16 weeks) observed in the MR images compared well with those observed on the corresponding histological sections.

Orthopedic Clinics of North America, Apr 1, 2012

Synthesis outweighs degradation Synthesis balanced by controlled matrix degradation Cartilage thi... more Synthesis outweighs degradation Synthesis balanced by controlled matrix degradation Cartilage thickness Thick cartilage that decreases with maturation Relatively thin articular cartilage Cartilage morphology 4 distinct zones: Zone of articular cartilage Zone of proliferation Zone of maturation Zone of calcification 3 distinct zones of uncalcified cartilage: Superficial zone Middle zone Deep zone Tidemark Absent initially but develops as the cartilage matures Well-demarcated lamina Calcified zone Absent Hypertrophied chondrocytes embedded in calcified matrix Vascularity Present but decreases with cartilage maturation Avascular Growth plate Morphology 4 distinct zones: Zone of resting Zone of proliferation Zone of maturation Zone of calcification Replaced by the primary tensile bone trabecula

Pediatric Radiology, Jan 6, 2005

Pulmonary thromboembolism (PTE) is uncommonly diagnosed in the pediatric patient, and indeed ofte... more Pulmonary thromboembolism (PTE) is uncommonly diagnosed in the pediatric patient, and indeed often only discovered on autopsy. The incidence of pediatric PTE depends upon the associated underlying disease, diagnostic tests used, and index of suspicion. Multiple risk factors can be found including: peripartum asphyxia, dyspnea, haemoptysis, chest pain, dehydration, septicemia, central venous lines (CVLs), trauma, surgery, ongoing hemolysis, vascular lesions, malignancy, renal disease, foreign bodies or, uncommonly, intracranial venous sinus thrombosis, burns, or nonbacterial thrombotic endocarditis. Other types of embolism can occur uncommonly in childhood and

The author has granted a nonexclusive Licence ailowing the National Library of Canada to reproduc... more The author has granted a nonexclusive Licence ailowing the National Library of Canada to reproduce, loan, distribute or sell copies of this thesis in microfom, paper or electronic formats. The author retains ownership of the copyright in this thesis. Neither the thesis nor substantial extracts fiom it may be printed or otherwise reproduced without the author's permission.

Springer eBooks, 2020

The unique structure of articular cartilage provides the intrinsic functional properties that ena... more The unique structure of articular cartilage provides the intrinsic functional properties that enable the knee joint to withstand and resist excessive compressive and biomechanical loads, facilitating almost frictionless knee movement. This chapter outlines the architectural and compositional features of articular cartilage. The relationships of chondrocytes to their pericellular environment, the territorial and interterritorial matrix domains as well as the zonal heterogeneity and compartmentalization from the articular surface to the subchondral bone are highlighted. Coupled with the biomechanical functions of articular cartilage, the lubrication mechanisms of knee articular cartilage along with the molecular structure, composition and concentration of the constituent lubricants critical in facilitating a smooth gliding movement of the opposing articular cartilage are discussed.

Osteoarthritis and Cartilage, Oct 1, 2017

Objective: Histopathological grading of osteochondral (OC) tissue is widely used in osteoarthriti... more Objective: Histopathological grading of osteochondral (OC) tissue is widely used in osteoarthritis (OA) research, and it is relatively common in post-surgery in vitro diagnostics. However, relying on thin tissue section, this approach includes a number of limitations, such as: (1) destructiveness, (2) sample processing artefacts, (3) 2D section does not represent spatial 3D structure and composition of the tissue, and (4) the final outcome is subjective. To overcome these limitations, we recently developed a contrastenhanced mCT (CEmCT) imaging technique to visualize the collagenous extracellular matrix (ECM) of articular cartilage (AC). In the present study, we demonstrate that histopathological scoring of OC tissue from CEmCT is feasible. Moreover, we establish a new, semi-quantitative OA mCT grading system for OC tissue. Results: Pathological features were clearly visualized in AC and subchondral bone (SB) with mCT and verified with histology, as demonstrated with image atlases. Comparison of histopathological grades (OARSI or severity (0e3)) across the characterization approaches, CEmCT and histology, excellent (0.92, 95% CI ¼ [0.84, 0.96], n ¼ 30) or fair (0.50, 95% CI ¼ [0.16, 0.74], n ¼ 27) intra-class correlations (ICC), respectively. A new mCT grading system was successfully established which achieved an excellent crossmethod (mCT vs histology) reader-to-reader intra-class correlation (0.78, 95% CI ¼ [0.58, 0.89], n ¼ 27). Conclusions: We demonstrated that histopathological information relevant to OA can reliably be obtained from CEmCT images. This new grading system could be used as a reference for 3D imaging and analysis techniques intended for volumetric evaluation of OA pathology in research and clinical applications.

Springer eBooks, 2020

Lifestyle modification and active physical therapy have been shown to be efficacious in cartilage... more Lifestyle modification and active physical therapy have been shown to be efficacious in cartilage repair following injury in reducing symptoms and possibly reducing disease progression to osteoarthritis (OA). Weight loss and moderate exercise are the most effective lifestyle modification modalities. Exercise can be classified as low impact exercise such as bicycling and high impact exercise such as running. For symptomatic patients, low impact exercises (such as on static bicycle) are preferable. Following knee articular cartilage injury, judicious application of cold in earliest phase to reduce inflammation and, later, heat to promote cartilage repair is used. Other physical modalities which may assist cartilage repair by facilitating fluid and metabolite flow through cartilage include continuous passive motion, low-energy laser therapy, and pulsed electromagnetic field (PEMF) therapy.

Osteoarthritis and Cartilage, 2018

Objective: Our aim is to establish methods for quantifying morphometric properties of calcified c... more Objective: Our aim is to establish methods for quantifying morphometric properties of calcified cartilage (CC) from micro-computed tomography (mCT). Furthermore, we evaluated the feasibility of these methods in investigating relationships between osteoarthritis (OA), tidemark surface morphology and open subchondral channels (OSCCs). Method: Samples (n ¼ 15) used in this study were harvested from human lateral tibial plateau (n ¼ 8). Conventional roughness and parameters assessing local 3-dimensional (3D) surface variations were used to quantify the surface morphology of the CC. Subchondral channel properties (percentage, density, size) were also calculated. As a reference, histological sections were evaluated using Histopathological osteoarthritis grading (OARSI) and thickness of CC and subchondral bone (SCB) was quantified. Results: OARSI grade correlated with a decrease in local 3D variations of the tidemark surface (amount of different surface patterns (r s ¼ À0.600, P ¼ 0.018), entropy of patterns (EP) (r s ¼ À0.648, P ¼ 0.018), homogeneity index (HI) (r s ¼ 0.555, P ¼ 0.032)) and tidemark roughness (TMR) (r s ¼ À0.579, P ¼ 0.024). Amount of different patterns (ADP) and EP associated with channel area fraction (CAF) (r p ¼ 0.876, P < 0.0001; r p ¼ 0.665, P ¼ 0.007, respectively) and channel density (CD) (r p ¼ 0.680, P ¼ 0.011; r p ¼ 0.582, P ¼ 0.023, respectively). TMR was associated with CAF (r p ¼ 0.926, P < 0.0001) and average channel size (r p ¼ 0.574, P ¼ 0.025). CC topography differed statistically significantly in early OA vs healthy samples. Conclusion: We introduced a m-CT image method to quantify 3D CC topography and perforations through CC. CC topography was associated with OARSI grade and OSCC properties; this suggests that the established methods can detect topographical changes in tidemark and CC perforations associated with OA.

Haemophilia, 2016

Rationale18F‐FDG‐PET/CT has a potential role in the early detection of haemophilic arthritis, at ... more Rationale18F‐FDG‐PET/CT has a potential role in the early detection of haemophilic arthritis, at a time when treatment may still avoid further joint degeneration. The purposes of this pilot study were to determine the ability of 18F‐FDG‐PET/CT to detect inflammatory changes associated with blood‐induced arthropathy in knees of a rabbit model.MethodsTen juvenile rabbits were imaged at baseline and weeks 5 and 17 post intraarticular autologous blood injections (ABI). Five rabbits in group 1 (G1) had ABI into the same knee joint every 2 weeks (total, eight injections). Five rabbits in group 2 (G2) had only two injections into the same knee, at weeks 5 and 17. Images were assessed visually and semi‐quantitatively by measuring maximal standardized uptake values (SUVmax) and standardized uptake ratio (SUR = SUVmax in affected knee/SUVmax in non‐affected knee).ResultsMore rabbits in G1 than G2 presented with positive chronic inflammatory synovial scores at week 17. Mean iron staining score...

1997 IEEE Ultrasonics Symposium Proceedings. An International Symposium (Cat. No.97CH36118), 1997

A system based on reconstituted articular cartilage is used to facilitate evaluation of noninvasi... more A system based on reconstituted articular cartilage is used to facilitate evaluation of noninvasive imaging methods such as ultrasound biomicroscopy (UBM) and magnetic resonance imaging (MRI) for assessment of osteoarthritis (OA). Chondrocytes from the superficial and deep layers of calf articular cartilage were isolated and cultured. Some cultures were treated with interleukin 1 (Il-1) and the effects on cartilage growth

Haemophilia : the official journal of the World Federation of Hemophilia, 2015

Ultrasmall paramagnetic iron oxide (USPIO)-enhanced MRI is promising for evaluating inflammation.... more Ultrasmall paramagnetic iron oxide (USPIO)-enhanced MRI is promising for evaluating inflammation. The aims of this study were to investigate the effect of USPIO on cartilage T1 and T2 mapping, and to evaluate a proposed rapid vs. conventional T2 map method for imaging cartilage in a blood-induced arthritis model. Knees of nine arthritic (induction by intra-articular autologous blood injection) and six control rabbits were imaged over time (baseline, weeks 1, 5, 10) by 1.5T MRI. All rabbits had USPIO (35-75 μmol Fe/kg)-enhanced MRI at each time point. T1 and T2 (conventional and rapid) maps and signal-to-noise ratios (SNR) were obtained pre- and post-USPIO administration. Cartilage biochemistry and histology were compared with MRI. Excellent correlations were noted between T1 map values and histologic scores at week 10 pre-USPIO (medial, r = 0.93, P = 0.0007; lateral, r = 0.87, P = 0.005) in the arthritic group, but not between T2 map and histology. Marginally and significant differe...

Pediatric Radiology, 2005

Pulmonary thromboembolism (PTE) is uncommonly diagnosed in the pediatric patient, and indeed ofte... more Pulmonary thromboembolism (PTE) is uncommonly diagnosed in the pediatric patient, and indeed often only discovered on autopsy. The incidence of pediatric PTE depends upon the associated underlying disease, diagnostic tests used, and index of suspicion. Multiple risk factors can be found including: peripartum asphyxia, dyspnea, haemoptysis, chest pain, dehydration, septicemia, central venous lines (CVLs), trauma, surgery, ongoing hemolysis, vascular lesions,

The Journal of rheumatology, 1995

To assess cartilage matrix quality variation by anatomical location and extent of osteoarthritis ... more To assess cartilage matrix quality variation by anatomical location and extent of osteoarthritis (OA) using quantitative magnetic resonance imaging (MRI) and to compare the anatomic MR morphologic features with corresponding histological findings. We studied 18 fully encapsulated right knee joints from a population of rhesus monkeys with a high incidence of degenerative arthritis resembling human OA. Relaxation times (T1 and T2) spin density, and cartilage thickness were determined along 8 contiguous anteroposterior segments of articular cartilage. Histological slides, prepared in the same plane as the MR image, were assessed for OA severity. Using a modification of Mankin's OA classification, each quadrant was grouped into normal (0), mild (1), moderate (2), or severe OA (3). Histopathological scores served as the standard and corresponding MR quadrants were classified accordingly. Cumulative results revealed a significant decrease in T1 relaxation time (p = 0.04) and an increa...

Orthopedic Clinics of North America, Apr 1, 2012

Springer eBooks, 2020

Cartilage is a dynamic tissue with enhanced complexity attributed to the existence of numerous de... more Cartilage is a dynamic tissue with enhanced complexity attributed to the existence of numerous developmental phases and overlap in phenotypic gene expression with related cell types. This chapter reviews the recent advances in molecular biology that illuminate the factors that drive and control articular cartilage growth and development. The objective is to provide a better understanding of the key molecular and genetic participants during the growth and development of articular-epiphyseal cartilage (AEC) and the epiphyseal growth plate (GP).

Articular cartilage serves as a lubricated, wear-resistant, friction-reducing self-maintaining ma... more Articular cartilage serves as a lubricated, wear-resistant, friction-reducing self-maintaining material that is slightly compressible to evenly distribute forces onto the bone. Articular cartilage macromolecular composition and architecture and its biomechanical properties are well adapted to withstand mechanical loads increasingly for a ten-decade lifetime. The three-dimensional orientation of the structural molecules and various levels of compartmentalization, namely, the horizontal zones from the articular surface to the underlying subchondral bone as well as interstitially from the surface of the chondrocytes, enable articular cartilage function by facilitating smooth knee movements by reducing friction and absorbing the impact of loading. Coupled with the biomechanical function of articular cartilage in its entirety, articular cartilage lubrication mechanisms provide almost frictionless surfaces between moving joints and do this throughout life adapting to both age and arthritic disease.

Osteoarthritis and Cartilage, Apr 1, 2016

Springer eBooks, 2020

Aging implies changes in articular cartilage cells and the surrounding extracellular matrix (ECM)... more Aging implies changes in articular cartilage cells and the surrounding extracellular matrix (ECM) that are reflective of metabolic changes related to time alone. For chondrocytes, these are genomic and intracytoplasmic changes that lessen their capacity to respond and control their extracellular environment; for the matrix, these are changes that lead to decreased hydration and increased brittleness of the tissue. Clinically, this can manifest as decreased capacity to withstand mechanical forces leading to degenerative arthritis.

Osteoarthritis and Cartilage, 2006

Objective: This study was performed to non-invasively visualize and characterize osteochondral (O... more Objective: This study was performed to non-invasively visualize and characterize osteochondral (OC) repair in ex vivo goat stifles using an 8 T magnetic resonance imaging (MRI) scanner and to compare the MR morphology with images obtained from 1.5 T, gross morphology and histology. Methods: Mature, neutered male goats were assigned to an 8-week (n Z 4) or 16-week (n Z 4) study period. Two cylindrical OC defects (7 mm diameter, full cartilage thickness and 1 mm into subchondral bone) were surgically created in the right stifle: one in the medial femoral condyle (MFC) and the other in the trochlear groove (TG). The implant matrices (non-woven or foam) were secured in the defect using a bottom anchored fixation device (FD). The contralateral left stifles served as time zero controls. At the day of necropsy, implants were placed at both defect sites (MFC and TG) on the normal left stifles. Following necropsy, the ex vivo goat stifles (intact and encapsulated) were disarticulated. Within 24 h postnecropsy, MR scans of the stifles along the mid-sagittal plane of the OC defect were acquired at 8 T and 1.5 T. MR relaxation times, T1 and T2, were measured at the region of repair tissue (RT) and adjacent native cartilage. Immediately after MR imaging, the stifles were dissected, grossly examined, and a sagittal OC block corresponding to the MR region of interest was prepared for formalin fixation. Results: The high-resolution MR images enabled visualization of cartilage and bone integrity surrounding the implant as well as delineating the margins of RT/implant matrix and the FD. On spin echo sequence, the RT variably appeared as high, intermediate or low MR signal intensity; whereas, the FD always appeared as low signal intensity. In general, the MR signal intensity of 8-week RT was slightly higher compared to 16week RT; however, there was no difference in RT morphology of stifles implanted with the non-woven matrix or foam matrix. Subchondral sclerosis appeared as low signal intensity. The 8 T MR images showed better delineation of the stifle tissues compared to the images acquired at 1.5 T. The T2 relaxation time of the RT appears to indicate (inconclusive due to small number of samples) a slight variation in the RT type between 8 weeks and 16 weeks. At both study times, the defects grossly appeared whitish to reddish but did not have the characteristic hyaline appearance typical of articular cartilage (AC). The gross appearance of the MFC and TG RT differed, which was predominantly mottled and recessed with fissuring of adjacent native AC in the MFC. Histologically, the RT of both 8-week and 16-week postsurgical defects predominantly comprised fibrovascular connective tissue with only few samples showing the presence of fibrocartilaginous and/or hypertrophic chondrocytes within the defect RT at 8 weeks. Also, compared to 8-week, the 16-week RT appeared to be more fibrotic. Conclusion: Using 8 T scanner, high-resolution MR images of ex vivo encapsulated goat stifles confirmed the capability of high-field MR imaging to distinguish the defect RT from the FD and adjacent joint tissues. The extent of OC repair and adjacent bone lesions (at 8 weeks and 16 weeks) observed in the MR images compared well with those observed on the corresponding histological sections.

Orthopedic Clinics of North America, Apr 1, 2012

Synthesis outweighs degradation Synthesis balanced by controlled matrix degradation Cartilage thi... more Synthesis outweighs degradation Synthesis balanced by controlled matrix degradation Cartilage thickness Thick cartilage that decreases with maturation Relatively thin articular cartilage Cartilage morphology 4 distinct zones: Zone of articular cartilage Zone of proliferation Zone of maturation Zone of calcification 3 distinct zones of uncalcified cartilage: Superficial zone Middle zone Deep zone Tidemark Absent initially but develops as the cartilage matures Well-demarcated lamina Calcified zone Absent Hypertrophied chondrocytes embedded in calcified matrix Vascularity Present but decreases with cartilage maturation Avascular Growth plate Morphology 4 distinct zones: Zone of resting Zone of proliferation Zone of maturation Zone of calcification Replaced by the primary tensile bone trabecula

Pediatric Radiology, Jan 6, 2005

Pulmonary thromboembolism (PTE) is uncommonly diagnosed in the pediatric patient, and indeed ofte... more Pulmonary thromboembolism (PTE) is uncommonly diagnosed in the pediatric patient, and indeed often only discovered on autopsy. The incidence of pediatric PTE depends upon the associated underlying disease, diagnostic tests used, and index of suspicion. Multiple risk factors can be found including: peripartum asphyxia, dyspnea, haemoptysis, chest pain, dehydration, septicemia, central venous lines (CVLs), trauma, surgery, ongoing hemolysis, vascular lesions, malignancy, renal disease, foreign bodies or, uncommonly, intracranial venous sinus thrombosis, burns, or nonbacterial thrombotic endocarditis. Other types of embolism can occur uncommonly in childhood and

The author has granted a nonexclusive Licence ailowing the National Library of Canada to reproduc... more The author has granted a nonexclusive Licence ailowing the National Library of Canada to reproduce, loan, distribute or sell copies of this thesis in microfom, paper or electronic formats. The author retains ownership of the copyright in this thesis. Neither the thesis nor substantial extracts fiom it may be printed or otherwise reproduced without the author's permission.

Springer eBooks, 2020

The unique structure of articular cartilage provides the intrinsic functional properties that ena... more The unique structure of articular cartilage provides the intrinsic functional properties that enable the knee joint to withstand and resist excessive compressive and biomechanical loads, facilitating almost frictionless knee movement. This chapter outlines the architectural and compositional features of articular cartilage. The relationships of chondrocytes to their pericellular environment, the territorial and interterritorial matrix domains as well as the zonal heterogeneity and compartmentalization from the articular surface to the subchondral bone are highlighted. Coupled with the biomechanical functions of articular cartilage, the lubrication mechanisms of knee articular cartilage along with the molecular structure, composition and concentration of the constituent lubricants critical in facilitating a smooth gliding movement of the opposing articular cartilage are discussed.

Osteoarthritis and Cartilage, Oct 1, 2017

Objective: Histopathological grading of osteochondral (OC) tissue is widely used in osteoarthriti... more Objective: Histopathological grading of osteochondral (OC) tissue is widely used in osteoarthritis (OA) research, and it is relatively common in post-surgery in vitro diagnostics. However, relying on thin tissue section, this approach includes a number of limitations, such as: (1) destructiveness, (2) sample processing artefacts, (3) 2D section does not represent spatial 3D structure and composition of the tissue, and (4) the final outcome is subjective. To overcome these limitations, we recently developed a contrastenhanced mCT (CEmCT) imaging technique to visualize the collagenous extracellular matrix (ECM) of articular cartilage (AC). In the present study, we demonstrate that histopathological scoring of OC tissue from CEmCT is feasible. Moreover, we establish a new, semi-quantitative OA mCT grading system for OC tissue. Results: Pathological features were clearly visualized in AC and subchondral bone (SB) with mCT and verified with histology, as demonstrated with image atlases. Comparison of histopathological grades (OARSI or severity (0e3)) across the characterization approaches, CEmCT and histology, excellent (0.92, 95% CI ¼ [0.84, 0.96], n ¼ 30) or fair (0.50, 95% CI ¼ [0.16, 0.74], n ¼ 27) intra-class correlations (ICC), respectively. A new mCT grading system was successfully established which achieved an excellent crossmethod (mCT vs histology) reader-to-reader intra-class correlation (0.78, 95% CI ¼ [0.58, 0.89], n ¼ 27). Conclusions: We demonstrated that histopathological information relevant to OA can reliably be obtained from CEmCT images. This new grading system could be used as a reference for 3D imaging and analysis techniques intended for volumetric evaluation of OA pathology in research and clinical applications.

Springer eBooks, 2020

Lifestyle modification and active physical therapy have been shown to be efficacious in cartilage... more Lifestyle modification and active physical therapy have been shown to be efficacious in cartilage repair following injury in reducing symptoms and possibly reducing disease progression to osteoarthritis (OA). Weight loss and moderate exercise are the most effective lifestyle modification modalities. Exercise can be classified as low impact exercise such as bicycling and high impact exercise such as running. For symptomatic patients, low impact exercises (such as on static bicycle) are preferable. Following knee articular cartilage injury, judicious application of cold in earliest phase to reduce inflammation and, later, heat to promote cartilage repair is used. Other physical modalities which may assist cartilage repair by facilitating fluid and metabolite flow through cartilage include continuous passive motion, low-energy laser therapy, and pulsed electromagnetic field (PEMF) therapy.

Osteoarthritis and Cartilage, 2018

Objective: Our aim is to establish methods for quantifying morphometric properties of calcified c... more Objective: Our aim is to establish methods for quantifying morphometric properties of calcified cartilage (CC) from micro-computed tomography (mCT). Furthermore, we evaluated the feasibility of these methods in investigating relationships between osteoarthritis (OA), tidemark surface morphology and open subchondral channels (OSCCs). Method: Samples (n ¼ 15) used in this study were harvested from human lateral tibial plateau (n ¼ 8). Conventional roughness and parameters assessing local 3-dimensional (3D) surface variations were used to quantify the surface morphology of the CC. Subchondral channel properties (percentage, density, size) were also calculated. As a reference, histological sections were evaluated using Histopathological osteoarthritis grading (OARSI) and thickness of CC and subchondral bone (SCB) was quantified. Results: OARSI grade correlated with a decrease in local 3D variations of the tidemark surface (amount of different surface patterns (r s ¼ À0.600, P ¼ 0.018), entropy of patterns (EP) (r s ¼ À0.648, P ¼ 0.018), homogeneity index (HI) (r s ¼ 0.555, P ¼ 0.032)) and tidemark roughness (TMR) (r s ¼ À0.579, P ¼ 0.024). Amount of different patterns (ADP) and EP associated with channel area fraction (CAF) (r p ¼ 0.876, P < 0.0001; r p ¼ 0.665, P ¼ 0.007, respectively) and channel density (CD) (r p ¼ 0.680, P ¼ 0.011; r p ¼ 0.582, P ¼ 0.023, respectively). TMR was associated with CAF (r p ¼ 0.926, P < 0.0001) and average channel size (r p ¼ 0.574, P ¼ 0.025). CC topography differed statistically significantly in early OA vs healthy samples. Conclusion: We introduced a m-CT image method to quantify 3D CC topography and perforations through CC. CC topography was associated with OARSI grade and OSCC properties; this suggests that the established methods can detect topographical changes in tidemark and CC perforations associated with OA.

Haemophilia, 2016

Rationale18F‐FDG‐PET/CT has a potential role in the early detection of haemophilic arthritis, at ... more Rationale18F‐FDG‐PET/CT has a potential role in the early detection of haemophilic arthritis, at a time when treatment may still avoid further joint degeneration. The purposes of this pilot study were to determine the ability of 18F‐FDG‐PET/CT to detect inflammatory changes associated with blood‐induced arthropathy in knees of a rabbit model.MethodsTen juvenile rabbits were imaged at baseline and weeks 5 and 17 post intraarticular autologous blood injections (ABI). Five rabbits in group 1 (G1) had ABI into the same knee joint every 2 weeks (total, eight injections). Five rabbits in group 2 (G2) had only two injections into the same knee, at weeks 5 and 17. Images were assessed visually and semi‐quantitatively by measuring maximal standardized uptake values (SUVmax) and standardized uptake ratio (SUR = SUVmax in affected knee/SUVmax in non‐affected knee).ResultsMore rabbits in G1 than G2 presented with positive chronic inflammatory synovial scores at week 17. Mean iron staining score...

1997 IEEE Ultrasonics Symposium Proceedings. An International Symposium (Cat. No.97CH36118), 1997

A system based on reconstituted articular cartilage is used to facilitate evaluation of noninvasi... more A system based on reconstituted articular cartilage is used to facilitate evaluation of noninvasive imaging methods such as ultrasound biomicroscopy (UBM) and magnetic resonance imaging (MRI) for assessment of osteoarthritis (OA). Chondrocytes from the superficial and deep layers of calf articular cartilage were isolated and cultured. Some cultures were treated with interleukin 1 (Il-1) and the effects on cartilage growth

Haemophilia : the official journal of the World Federation of Hemophilia, 2015

Ultrasmall paramagnetic iron oxide (USPIO)-enhanced MRI is promising for evaluating inflammation.... more Ultrasmall paramagnetic iron oxide (USPIO)-enhanced MRI is promising for evaluating inflammation. The aims of this study were to investigate the effect of USPIO on cartilage T1 and T2 mapping, and to evaluate a proposed rapid vs. conventional T2 map method for imaging cartilage in a blood-induced arthritis model. Knees of nine arthritic (induction by intra-articular autologous blood injection) and six control rabbits were imaged over time (baseline, weeks 1, 5, 10) by 1.5T MRI. All rabbits had USPIO (35-75 μmol Fe/kg)-enhanced MRI at each time point. T1 and T2 (conventional and rapid) maps and signal-to-noise ratios (SNR) were obtained pre- and post-USPIO administration. Cartilage biochemistry and histology were compared with MRI. Excellent correlations were noted between T1 map values and histologic scores at week 10 pre-USPIO (medial, r = 0.93, P = 0.0007; lateral, r = 0.87, P = 0.005) in the arthritic group, but not between T2 map and histology. Marginally and significant differe...

Pediatric Radiology, 2005

Pulmonary thromboembolism (PTE) is uncommonly diagnosed in the pediatric patient, and indeed ofte... more Pulmonary thromboembolism (PTE) is uncommonly diagnosed in the pediatric patient, and indeed often only discovered on autopsy. The incidence of pediatric PTE depends upon the associated underlying disease, diagnostic tests used, and index of suspicion. Multiple risk factors can be found including: peripartum asphyxia, dyspnea, haemoptysis, chest pain, dehydration, septicemia, central venous lines (CVLs), trauma, surgery, ongoing hemolysis, vascular lesions,

The Journal of rheumatology, 1995

To assess cartilage matrix quality variation by anatomical location and extent of osteoarthritis ... more To assess cartilage matrix quality variation by anatomical location and extent of osteoarthritis (OA) using quantitative magnetic resonance imaging (MRI) and to compare the anatomic MR morphologic features with corresponding histological findings. We studied 18 fully encapsulated right knee joints from a population of rhesus monkeys with a high incidence of degenerative arthritis resembling human OA. Relaxation times (T1 and T2) spin density, and cartilage thickness were determined along 8 contiguous anteroposterior segments of articular cartilage. Histological slides, prepared in the same plane as the MR image, were assessed for OA severity. Using a modification of Mankin's OA classification, each quadrant was grouped into normal (0), mild (1), moderate (2), or severe OA (3). Histopathological scores served as the standard and corresponding MR quadrants were classified accordingly. Cumulative results revealed a significant decrease in T1 relaxation time (p = 0.04) and an increa...