Harpal K Gahunia

University of Chile, CiudadSantiago, Santiago, Chile

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Publications (22)43.75 Total impact

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    ABSTRACT: Blood-oxygen-level-dependent (BOLD) MRI has the potential to identify regions of early hypoxic and vascular joint changes in inflammatory arthritis. There is no standard protocol for analysis of BOLD MRI measurements in musculoskeletal disorders. To optimize the following BOLD MRI reading parameters: (1) statistical threshold values (low, r > 0.01 versus high, r > 0.2); (2) summary measures of BOLD contrast (percentage of activated voxels [PT%] versus percentage signal difference between on-and-off signal intensities [diff_on_off]); and (3) direction of BOLD response (positive, negative and positive + negative). Using BOLD MRI protocols at 1.5 T, arthritic (n = 21) and contralateral (n = 21) knees of 21 juvenile rabbits were imaged at baseline and on days 1, 14 and 28 after a unilateral intra-articular injection of carrageenan. Nine non-injected rabbits served as external control knees (n = 18). By comparing arthritic to contralateral knees, receiver operating characteristic curves were used to determine diagnostic accuracy. Using diff_on_off and positive + negative responses, a threshold of r > 0.01 was more accurate than r > 0.2 (P = 0.03 at day 28). Comparison of summary measures yielded no statistically significant difference (P > 0.05). Although positive + negative (AUC = 0.86 at day 28) and negative responses (AUC = 0.90 at day 28) for PT% were the most diagnostically accurate, positive + negative responses for diff_on_off (AUC = 0.78 at day 28) also had acceptable accuracy. The most clinically relevant reading parameters included a lower threshold of r > 0.01 and a positive + negative BOLD response. We propose that diff_on_off is a more clinically relevant summary measure of BOLD MRI, while PT% can be used as an ancillary measure.
    Pediatric Radiology 12/2013; · 1.57 Impact Factor
  • Harpal K Gahunia, Kenneth P H Pritzker
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    ABSTRACT: This review primarily focuses on how the macromolecular composition and architecture of articular cartilage and its unique biomechanical properties play a pivotal role in the ability of articular cartilage to withstand mechanical loads several magnitudes higher than the weight of the individual. Current findings on short-term and long-term effects of exercise on human articular cartilage are reviewed, and the importance of appropriate exercises for individuals with normal and diseased or aberrated cartilage is discussed.
    Orthopedic Clinics of North America 04/2012; 43(2):187-99, v. · 1.25 Impact Factor
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    ABSTRACT: In this article, development of articular cartilage and endochondral ossification is reviewed, from the perspective of both morphologic aspects of histogenesis and molecular biology, particularly with respect to key signaling molecules and extracellular matrix components most active in cartilage development. The current understanding of the roles of transforming growth factor β and associated signaling molecules, bone morphogenic proteins, and molecules of the Wnt-β catenin system in chondrogenesis are described. Articular cartilage development is a highly conserved complex biological process that is dynamic and robust in nature, which proceeds well without incident or failure in all joints of most young growing individuals.
    Orthopedic Clinics of North America 04/2012; 43(2):155-71, v. · 1.25 Impact Factor
  • Harpal K Gahunia
    Orthopedic Clinics of North America 04/2012; 43(2):ix-x. · 1.25 Impact Factor
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    ABSTRACT: Because of the ability of blood-oxygen-level-dependent (BOLD) MRI to assess blood oxygenation changes within the microvasculature, this technique holds potential for evaluating early perisynovial changes in inflammatory arthritis. To evaluate the feasibility of BOLD MRI to detect interval perisynovial changes in knees of rabbits with inflammatory arthritis. Rabbit knees were injected with albumin (n=9) or saline (n=6) intra-articularly, or were not injected (control knees, n=9). Except for two rabbits (albumin-injected, n=2 knees; saline-injected, n=2 knees) that unexpectedly died on days 7 and 21 of the experiment, respectively, all other animals were scanned with BOLD MRI on days 0, 1, 7, 14, 21 and 28 after induction of arthritis. T2*-weighted gradient-echo MRI was performed during alternate 30 s of normoxia/hyperoxia. BOLD MRI measurements were compared with clinical, laboratory and histological markers. Percentage of activated voxels was significantly greater in albumin-injected knees than in contralateral saline-injected knees (P=0.04). For albumin-injected knees (P<0.05) and among different categories of knees (P=0.009), the percentage of activated BOLD voxels varied over time. A quadratic curve for on-and-off BOLD difference was delineated for albumin- and saline-injected knees over time (albumin-injected, P=0.047; saline-injected, P=0.009). A trend toward a significant difference in synovial histological scores between albumin-injected and saline-injected knees was noted only for acute scores (P=0.07). As a proof of concept, BOLD MRI can depict perisynovial changes during progression of experimental arthritis.
    Pediatric Radiology 08/2011; 42(1):63-75. · 1.57 Impact Factor
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    ABSTRACT: PURPOSE When recognized and treated early, symptoms of hemophilia can be greatly reduced and joint degeneration avoided. Treatment however, must begin before macroscopic lesions develop in the joint cartilage. The study objective was to determine the effects of a limited (n=2, Group 2) vs. a more extensive (n=8, Group 1) number of joint bleeds vs. no prior bleeds (Group 3) on the development of knee joint cartilage degeneration in a rabbit model by using T1 and T2 maps as surrogate imaging techniques for assessment of early cartilage damage. METHOD AND MATERIALS Juvenile male rabbits (n=21) were randomized into 3 groups (n=9: Groups 1 and 2; n=3 Group 3) and subject to autologous blood injections in one knee to simulate hemophilic arthropathy. Group 1: injections on week 1, 5, 7, 9, 11, 13, 15 and 17; Group 2: injections on week 1 and 17; Group 3: no injections. Rabbits were MR imaged (unenhanced T1 and short TR T2 map) at 1.5 T on weeks 0, 5 and 17 of the study, then euthanized on week 17. T1 maps were compared with cartilage proteoglycan content and T2 map with the degree of collagen organization [polarized light microscopy (picrosirus staining)] in corresponding histologic specimens. RESULTS On week 5, a borderline difference was noted between groups 1 and 3 for T2 (P=0.056) and T1 map values (P=0.055) suggesting that even a minimal amount of intra-articular bleeds causes functional cartilage changes. On week 17, significant differences were noted between groups 1 and 3 for T2 (lateral femoral condyle, P<0.0001; medial femoral condyle, P=0.01) and T1 (lateral femoral condyle, P=0.03; medial femoral condyle, P=0.055) map values suggesting that the interval of time plays a role in determining presence of cartilage changes. T1 and T2 maps correlated well with corresponding histology. CONCLUSION Even minimal amounts of intra-articular bleeds cause micro-structural cartilage deterioration within the knee joint. Interval of time between the bleeding episode and imaging is a determinant of cartilage damage. Both T1 and T2 maps can be used as surrogate imaging techniques for assessment and follow-up of early cartilage changes in hemophilic joints. CLINICAL RELEVANCE/APPLICATION The use of T2 and T1 mapping as surrogate imaging techniques for assessment of early cartilage changes can assist physicians as a cost-effective prophylaxis for hemophilic arthropathy.
    Radiological Society of North America 2010 Scientific Assembly and Annual Meeting; 12/2010
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    ABSTRACT: Human growth is a multifactorial trait influenced by environmental, hormonal, and genetic factors. Although it is clear that multiple factors contribute to an individual's final height and limb development, genetic factors play a crucial role. One such gene is the short stature homeobox ( SHOX) containing gene. Knowledge about the SHOX gene has rapidly increased since its discovery in 1997, and we now know that SHOX haploinsufficiency affects the development of the extremities and is an important cause of short stature. Currently, SHOX mutations occur with an estimated incidence of roughly 1 in 1000 newborns, making mutations of this gene one of the most common genetic defects associated with growth failure and skeletal deformities. Heterozygous mutations of SHOX have been implicated in patients with Madelung's deformity, Leri-Weill dyschondrosteosis (77%), Turner's syndrome (66%), and idiopathic short stature (3%), and homozygous mutations of SHOX gene have been identified in patients with Langer's mesomelic dysplasia (100%). Recognition of the early radiographic features encountered in SHOX haploinsufficiency maybe pivotal for the diagnosis. In this article, we summarize the genetic and clinical features of the various SHOX haploinsufficiency-associated disorders. We present the characteristic imaging features of these disorders and the results of growth hormone treatment trials.
    Seminars in Musculoskeletal Radiology 10/2009; 13(3):236-54. · 1.40 Impact Factor
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    ABSTRACT: PURPOSE To measure the association between BOLD MRI and intra-articular pO2, and between Gd-DTPA dynamic contrast-enhanced (DCE) MRI and intra-articular blood flow obtained in real-time through fiberoptic polarographic probes (reference standard measures for oxygen extraction and microvascular blood flow within perisynovial tissues, respectively) at different timepoints of the arthritis course. METHOD AND MATERIALS We imaged arthritic and contralateral non-arthritic knee joints of 7 non-treated juvenile rabbits respectively on baseline, days 1, 14 and 28 after induction of arthritis by intra-articular injection of Carrageenin with BOLD and DCE MRI at 1.5 T. Additional 3 non-injected rabbits served as control subjects. Intra-articular temperature, pO2 and BPU (arbitrary blood flow measure) were obtained in real-time through polarographic probes (Oxford Optronix, London, England) while BOLD (on- and off- signal intensity difference of activated voxels) and DCE (maximum signal intensity, maximum uptake rate, maximum time-to-peak enhancement [TTP]) MR images were acquired. RESULTS The association between BOLD MRI measurements and intra-articular pO2 was significant (P=0.02 and P=0.04, respectively) but moderate (r=0.60 and r=0.59, respectively) in arthritic knees using either 100% O2 (stimulus) and 30-second interval paradigms of normoxia (off) and hyperoxia (on) or using 95% O2/5% CO2 (stimulus) and 60-second interval paradigms. BOLD signal tended to decrease in acute arthritis (day 1 after induction) reflecting the decrease in intra-articular venous pO2 in this stage of arthritis. Subsequently, the BOLD signal tended to return to baseline levels. A significant correlation (r=0.71, P=0.007) between TTP and intra-articular blood flow was noted over time. CONCLUSION In spite of moderate associations noted between BOLD MRI measurements and intra-articular pO2 at 1.5 T, both BOLD and DCE MRI hold potential as non-invasive surrogate measures for assessment of early hypoxic and inflammatory changes in arthritis. CLINICAL RELEVANCE/APPLICATION BOLD and DCE MRI may provide information on oxygenation and microvascularity of the joint holding potential as non-invasive diagnostic adjuncts to clinical and laboratory assessments in arthritis.
    Radiological Society of North America 2007 Scientific Assembly and Annual Meeting; 11/2007
  • Osteoarthritis and Cartilage 01/2006; 14. · 4.26 Impact Factor
  • Paul S Babyn, Harpal K Gahunia, Patricia Massicotte
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    ABSTRACT: 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 need to be recognized, as the required treatment will vary. These include pulmonary cytolytic thrombi, foreign bodies, tumor and septic emboli, and post-traumatic fat emboli. No single noninvasive test for pulmonary embolism is both sensitive and specific. A combination of diagnostic procedures must be used to identify suspect or confirmed cases of PTE. This article reviews the risk factors, clinical presentation and treatment of pulmonary embolism in children. It also highlights the current diagnostic tools and protocols used to evaluate pulmonary embolism in pediatric patients.
    Pediatric Radiology 04/2005; 35(3):258-74. · 1.57 Impact Factor
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    ABSTRACT: Severe acute respiratory syndrome (SARS) is a recently recognized condition of viral origin associated with substantial morbidity and mortality rates in adults. Little information is available on its radiologic manifestations in children. The goal of this study was to characterize the radiographic presentation of children with SARS. We abstracted data (n=62) on the radiologic appearance and course of SARS in pediatric patients with suspect (n=25) or probable (n=37) SARS, diagnosed in five hospital sites located in three cities: Toronto, Singapore, and Hong Kong. Available chest radiographs and thoracic CTs were reviewed for the presence of the following radiographic findings: airspace disease, air bronchograms, airways inflammation and peribronchial thickening, interstitial disease, pleural effusion, and hilar adenopathy. A total of 62 patients (suspect=25, probable=37) were evaluated for SARS. Patient ages ranged from 5.5 months to 17 years and 11.5 months (average, 6 years and 10 months) with a female-to-male ratio of 32:30. Forty-one patients (66.1%) were in close contact with other probable, suspect, or quarantined cases; 10 patients (16.1%) had recently traveled to WHO-designated affected areas within 10 days; and 7 patients (11.2%) were transferred from other hospitals that had SARS patients. Three patients, who did not have close/hospital contact or travel history to affected areas, were classified as SARS cases based on their clinical signs and symptoms and on the fact that they were living in an endemic area. The most prominent clinical presentations were fever, with a temperature over 38 degrees C (100%), cough (62.9%), rhinorrhea (22.6%), myalgia (17.7%), chills (14.5%), and headache (11.3%). Other findings included sore throat (9.7%), gastrointestinal symptoms (9.7%), rigor (8.1%), and lethargy (6.5%). In general, fever and cough were the most common clinical presentations amongst younger pediatric SARS cases (age<10 years), whereas, in addition to these symptoms, headache, myalgia, sore throat, chills, and/or rigor were common in older patients (age>/=10 years). The chest radiographs of 35.5% of patients were normal. The most prominent radiological findings that were observed in the remaining patients were areas of consolidation (45.2%), often peripheral with multifocal lesions in 22.6%. Peribronchial thickening was noted on chest radiographs of 14.5% of patients. Pleural effusion was observed only in one patient (age 17 years and 11.5 months), whereas interstitial disease was not observed in any patient. In pediatric cases, SARS manifests with nonspecific radiographic features making radiological differentiation difficult, especially from other commonly encountered childhood respiratory viral illnesses causing airspace disease. The radiographic presentation of suspected SARS cases ranged from normal to mild perihilar peribronchial thickening. The radiographic presentations, as expected, were relatively more pronounced in the SARS probable cases.
    Pediatric Radiology 02/2004; 34(1):47-58. · 1.57 Impact Factor
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    ABSTRACT: Fluorescent biomolecules within cartilage matrix can be used as specific markers of cartilage metabolism. While establishing the protocol to evaluate mature collagen crosslinks in articular cartilage (AC) associated with maturation, aging, and osteoarthritis, chromatographic analysis of the crosslinks also revealed an apparently novel fluorescent peak. Preliminary investigation of this compound (now abbreviated DDP) in various tissues from rabbits, calves, chickens, and humans showed that this compound is AC-specific. We aimed to isolate, purify, and identify this fluorescent compound. Fully encapsulated, bovine metacarpophalangeal joints (n = 350, age < 2 years) were used as the source for AC. DDP was isolated and purified by reverse phase high pressure liquid chromatography, and its elution was monitored using a fluorescence detector at excitation lambda = 306 nm, and emission lambda = 395 nm. The liquid phase of DDP was characterized by mass spectrometry and nuclear magnetic resonance spectroscopy. DDP solution (5.7 microg/microl) was crystallized in 100% deuterated methanol and the DDP crystal was characterized by single crystal x-ray diffraction. From bulk preparations, 12 pg (58 nmol) per gram dried AC of the novel compound was isolated and purified. Analytical techniques to identify this AC-specific compound, 2,6-dimethyldifuro-8-pyrone, corroborate and confirm its molecular structure and atomic connectivity in both liquid and solid phase. DDP is a symmetrical aromatic compound with molecular weight 204, molecular forrmula C11H8O4, and a molar extinction coefficient 4,700 M(-1) at maximal UV absorption (lambda = 306 nm). 2,6-dimethyldifuro-8-pyrone (DDP) is a novel cartilage-specific compound that could have potential application as a unique biochemical marker in joint diseases involving articular cartilage degradation.
    The Journal of Rheumatology 01/2002; 29(1):147-53. · 3.26 Impact Factor
  • Harpal K Gahunia, Reinhold Vieth, Kenneth Pritzker
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    ABSTRACT: To investigate the presence of and quantify 2,6-dimethyldifuro-8-pyrone (DDP), a novel fluorescent compound identified as in various calf, rabbit, and human tissue/fluid samples, to determine the DDP level in articular cartilage (AC) laminae, and to investigate the changes in cartilage DDP content with cartilage maturation. Samples were obtained from calf (< 2 years), rabbit (< 2 weeks to 2 years) or human AC and synovial fluid (SF) as well as other non-cartilaginous tissues. SF and tissue samples were hydrolyzed with 6 M HCl (24 hours at 110 degrees C), lyophilized, and dissolved in HPLC mobile phase. DDP and collagen crosslink peaks were measured using a fluorescence detector at excitation and emission wavelengths of 295 and 395 nm, respectively. DDP was detected from calf metacarpophalangeal joint AC (362 +/- 48 pmol/mg dry weight), SF (4.5 +/- 0.3 pmol/microl SF), and intervertebral disc (24 +/- 4 pmol/mg). DDP was not detected in calf ligament, tendon, bone, ocular lens, cornea, or elastic cartilage. The DDP amount was greater in mid-deep cartilage lamina (448 +/- 63 pmol/mg) than superficial-mid lamina (129 +/- 52 pmol/mg) (p = 0.008). DDP level decreased with maturation in rabbit knee joint AC from 185 +/- 40 (< 2 weeks) to 27 +/- 3 (2 years) pmol/mg dry weight. DDP was not detected in adult rabbit ligament, tendon, meniscus, or bone. DDP was detected in human knee joint AC and SF. The DDP level in osteoarthritic lesions was present in lower concentrations (range: 0 to 96 pmol/mg dried AC) compared to intact AC (range: 63 to 236 pmol/mg) of the same knee. DDP is a hyaline cartilage specific compound present in all articular cartilage samples from various articulating joints/animal species. DDP level increases with AC depth and decreases with cartilage maturation. DDP is a potential indicator of cartilage metabolism during normal growth, ageing, and cartilage disease.
    The Journal of Rheumatology 01/2002; 29(1):154-60. · 3.26 Impact Factor
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    ABSTRACT: MRI of the cartilaginous epiphysis (CE) of piglet femoral head was performed after ischemic damage to study the changes in the CE found on MRI and to correlate these changes with histologic findings. Avascular necrosis of the femoral head was induced with a suture ligature in nine piglets; one piglet was killed postoperatively on day 3 and on weeks 1, 2, 3, 4, 6, 7, and 8 (two piglets were killed on week 3). MRI of the ischemic and contralateral nonischemic hip joints were obtained with a 60-mm field of view (low resolution MRI). Biopsy cores of the femoral heads were imaged with a 15-mm field of view (high resolution MRI) and correlated with histologic sections. The CE for all operated hips, except for the 3-day postoperative specimen, showed evidence of ischemic changes on histologic assessment; the severity of damage increased with time. The MRI appearance of ischemic and nonischemic CE was clearly different by 2 weeks after the operation. No trilaminar signal pattern was evident in the high resolution T2-weighted (T2W) imaging of the ischemic CE from 2 weeks after the operation. In the 3- to 8-week postoperative specimens, focal areas of low signal intensity on high resolution T1-weighted (T1W) and T2W imaging corresponded to the areas of chondronecrosis found on histologic assessment. The regions of high signal intensity on T2W imaging corresponded to the areas of chondrocyte clusters with increased safranin-O staining. High resolution MRI can demonstrate changes in the CE associated with ischemic injury and may have a role in the assessment of the CE and its development after ischemic injury.
    Journal of Magnetic Resonance Imaging 01/1998; 8(3):717-23. · 2.57 Impact Factor
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    ABSTRACT: 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 were studied. On days 21, 35, and 56 the cartilage cultures were examined using UBM, MRI, and histology. Cartilage thickness measured using UBM, MRI, and histology were similar with the correlation coefficients of 0.982 (P<0.0001) and 0.998 (P<0.0001) respectively. Comparisons of the UBM images with histology and MRI are presented and potential application of the real time UBM imaging of cartilage is discussed
    Ultrasonics Symposium, 1997. Proceedings., 1997 IEEE; 11/1997
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    ABSTRACT: The aim of this study was to determine whether high-resolution magnetic resonance (MR) imaging could differentiate epiphyseal and articular cartilage in the cartilaginous epiphysis and demonstrate its developmental changes. T1- and T2-weighted (T1W and T2W) spin-echo sequences at 50-mm field of view (FOV) of hip joints were obtained from 14 piglets (newborn to 6 months). Subsequently, high-resolution MR images (15-mm FOV) of a biopsy core of the proximal femoral cartilaginous epiphysis were correlated with histology. Newborn cartilaginous epiphysis demonstrated homogeneous signal intensity on T1W and T2W imaging with abundant cartilage canals. From 2 weeks of age, the cartilaginous epiphysis showed a diminution of cartilage canals, with three zones evident on T2W imaging consisting of a low-signal middle zone separating two higher signal zones. Histologic evaluation demonstrated four distinct morphologic laminas with a decrease in overall cartilage thickness with age. The laminas were not as well defined in the newborn compared with the older piglets. No simple correlation was found between the MR zonal pattern and the morphological laminas on histology. No distinct demarcation between the articular cartilage and epiphyseal cartilage was present. MR can visualize cartilage canals and demonstrate changes in the cartilaginous epiphysis that occur with maturation. What component of the cartilaginous epiphysis that accounts for the MR differences seen between newborn and older piglets remains unclear.
    Journal of Magnetic Resonance Imaging 01/1996; 6(1):172-9. · 2.57 Impact Factor
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    ABSTRACT: A high frequency sonographic technique-ultrasound backscatter microscopy-was used to visualize the subsurface structure of immature porcine articular cartilage from the knee joint. In 20-week-old pigs, all parts that were scanned, except the weight-bearing regions of the femoral condyles, demonstrated heterogeneous ultrasound backscatter characteristics within the articular cartilage. A trilaminar pattern consisting of hypoechoic, hyperechoic, and anechoic layers ranging from superficial to deep generally was observed, except in the weight-bearing regions of the femoral condyles, where a homogeneous anechoic pattern was seen. In the younger pigs (6 and 10 weeks old), the trilaminar backscatter pattern was not observed. Small, highly echogenic structures that correlated with vascular channels in histologic assessment were observed frequently in the cartilage of younger pigs, but they were seldom present in the cartilage of 20-week-old pigs. Structural details, such as disruption of the subchondral bone and presence of a thickened fibrous layer on the articular surface at the chondrosynovial junction, also were detected with the ultrasound backscatter microscope. We concluded that high frequency ultrasound can be used to visualize the subsurface structure of immature articular cartilage and some of its developmental changes. Further research is required to explain the mechanism underlying the observed backscatter characteristics of immature articular cartilage and to study its potential for the imaging of pathologic changes.
    Journal of Orthopaedic Research 12/1995; 13(6):963-70. · 2.88 Impact Factor
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    ABSTRACT: Although osteoarthritis (OA) is the most common cause of articular skeletal disability in humans, assessing progression (staging) with noninvasive methods remains a major clinical problem. Using the rhesus macaque animal model, the objective of this study was to compare OA staging by noninvasive magnetic resonance imaging (MRI) against gross pathology and histopathology. Right knee joints from 18 rhesus macaques were used in this study. Using a four-point ordinal scale for each of the above-mentioned modalities, the lateral and medial femoral condyle and tibial plateau of each knee joint was independently scored for OA severity, i.e. normal, mild OA, moderate OA and severe OA. Correlation between each staging system was performed using Stuart's Tau-c correlation coefficient. By our criteria, MRI staging correlated as well with gross pathology (tau = 0.75) and histopathology (tau = 0.80) as did gross pathology with histopathology (tau = 0.78). Our study shows that MRI is a promising noninvasive modality to evaluate the severity of OA. MRI appears to be sensitive for demarcating the presence and extent of focal OA cartilage lesions. However, at this time, while MRI is sensitive for detecting OA change it cannot distinguish between certain lesions such as superficial cartilage matrix fibrillation and hypertrophy both of which show elevated signal intensity.
    Osteoarthritis and Cartilage 10/1995; 3(3):169-80. · 4.26 Impact Factor
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    ABSTRACT: 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 increase in T2 relaxation time (p = 0.03) in the mild and severe OA groups, respectively. Statistically significant changes in spin density and cartilage thickness measurements were not observed. MR signal intensity abnormalities in selected regions of interest were demarcated and studied histologically. Regions with histological proliferating chondrocytes or fibrillated cartilage showed bright signal intensity on MR images (TR = 3000 ms; TE = 10 ms) and corresponded with elevated T1 and T2 values. Histological regions of collagen condensation showed low signal intensity on MR images (TR = 3000 ms; TE = 10 ms) and corresponded with decreased T1 and T2 relaxation times. Topological quantitative MRI relaxation time assessment demonstrates increasing cartilage matrix quality variation with OA progression.
    The Journal of Rheumatology 10/1995; 22(9):1747-56. · 3.26 Impact Factor
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    ABSTRACT: Osteoarthritis (OA) is a disorder which results in the destruction of the articular cartilage and the remodeling of the subchondral bone in synovial joints. We have analyzed the cartilage collagen from normal and osteoarthritic free-ranging rhesus monkeys from the Cayo Santiago colony. The cartilage samples were assigned a severity score based on histological staging system and were divided into four groups (normals, mild OA, moderate OA and severe OA). After a 4.0 M guanidinium chloride (GuCl) extraction, the remainder of the cartilage was digested with pepsin and the collagen was salt precipitated at 2.5 M and 4.3 M NaCl. The GuCl solubility of the osteoarthritic cartilage increased compared to normals. Collagen extractability by GuCl also increased with the severity of disease. Pepsin digestion followed by salt precipitation shows that collagen from rhesus osteoarthritis cartilage is more easily extracted than from normal cartilage. With an anti-type I collagen antibody we have detected the presence of type I collagen in the severe OA cartilage samples but not in the milder OA groups or in normal cartilage. Total collagen content decreases with severity of OA, which is not due to changes in propyl hydroxylation because examination of collagen hydroxylation, based on hydroxyproline analysis, shows no difference between OA and normal cartilage.
    Osteoarthritis and Cartilage 01/1995; 2(4):227-34. · 4.26 Impact Factor

Publication Stats

172 Citations
43.75 Total Impact Points

Institutions

  • 2012
    • University of Chile
      CiudadSantiago, Santiago, Chile
  • 1993–2012
    • University of Toronto
      Toronto, Ontario, Canada
  • 1996–2009
    • SickKids
      • Department of Diagnostic Imaging
      Toronto, Ontario, Canada
  • 1995–2002
    • Mount Sinai Hospital, Toronto
      • Department of Pathology and Laboratory Medicine
      Toronto, Ontario, Canada
    • Samuel Lunenfeld Research Institute
      Toronto, Ontario, Canada