Andy Kin On Wong

Diagnosis and incidence of cardiac injury in children with blunt thoracic trauma

Over a 20-month period, we prospectively studied 41 children with blunt thoracic trauma (BTT) to determine the incidence and morbidity of cardiac injury in this population. Four patients died, and the data were incomplete in 10, leaving 27 for analysis. Serial electrocardiograms (ECG) were abnormal in 36% of the patients studied, serial creatine phosphokinase isoenzyme (CK-MB) ratios were elevated in 31%, echocardiogram showed septal dysfunction in 14%, and pyrophosphate scan showed grade 1 uptake in 14%. There was poor correlation among tests, since only four patients had more than one abnormal test. There was no significant difference in Injury Severity Score or Thoracic Abbreviated Injury Scale between patients with and without abnormal investigations. No patient in the study developed arrhythmias or cardiac failure. In 13 trauma-related deaths undergoing autopsy over the same period, including the four with thoracic trauma, none had evidence of cardiac injury. These results indicate a striking lack of consistency in the diagnosis of posttraumatic cardiac injury in children using standard investigations. The absence of adverse cardiac events in surviving patients and the lack of autopsy evidence of cardiac injury in the trauma deaths suggest that the actual incidence and clinical significance of these lesions in children is lower than generally reported. Children with BTT should be followed clinically, and reliance on screening tests should be avoided.

Improving Reliability of pQCT-Derived Muscle Area and Density Measures Using a Watershed Algorithm for Muscle and Fat Segmentation

In peripheral quantitative computed tomography scans of the calf muscles, segmentation of muscles from subcutaneous fat is challenged by muscle fat infiltration. Threshold-based edge detection segmentation by manufacturer software fails when muscle boundaries are not smooth. This study compared the test-retest precision error for muscle-fat segmentation using the threshold-based edge detection method vs manual segmentation guided by the watershed algorithm. Three clinical populations were investigated: younger adults, older adults, and adults with spinal cord injury (SCI). The watershed segmentation method yielded lower precision error (1.18%-2.01%) and higher (p<0.001) muscle density values (70.2±9.2 mg/cm3) compared with threshold-based edge detection segmentation (1.77%-4.06% error, 67.4±10.3 mg/cm3). This was particularly true for adults with SCI (precision error improved by 1.56% and 2.64% for muscle area and density, respectively). However, both methods still provided acceptable precision with error well under 5%. Bland-Altman analyses showed that the major discrepancies between the segmentation methods were found mostly among participants with SCI where more muscle fat infiltration was present. When examining a population where fatty infiltration into muscle is expected, the watershed algorithm is recommended for muscle density and area measurement to enable the detection of smaller change effect sizes.

Quantitative analysis of subchondral sclerosis of the tibia by bone texture parameters in knee radiographs: site-specific relationships with joint space width

OBJECTIVES To determine the ability of radiographic bone texture (BTX) parameters to quantify subchondral tibia sclerosis and to examine clinical relevance for assessing osteoarthritis (OA) progression. We examined the relationship between BTX parameters and each of (1) location-specific joint space width (JSW) [JSW(x)] and minimum JSW (mJSW) of the affected compartment, and (2) knee alignment (KA) angle in knee radiographs of participants undergoing total knee arthroplasty (TKA). DESIGN Digitized fixed-flexion knee radiographs were analyzed for run-length and topological BTX parameters in a subchondral region using an algorithm. Medial JSW(x) was computed at x=0.200, 0.225, 0.250 and 0.275 according to a coordinate system defined by anatomic landmarks. mJSW was determined for medial and lateral compartment lesions. KA angles were determined from radiographs using an anatomic landmark-guided algorithm. JSW measures and the magnitude of knee malalignment were each correlated with BTX parameters. Reproducibility of BTX parameters was measured by root-mean square coefficients of variation (RMSCV%). RESULTS Run-length BTX parameters were highly reproducible (RMSCV%<1%) while topological parameters showed poorer reproducibility (>5%). In TKA participants (17 women, 13 men; age: 66+/-9 years; body mass index (BMI): 31+/-6 kg m(-2); WOMAC: 41.5+/-16.1; Kellgren-Lawrence score mode: 4), reduced trabecular spacing (Tb.Sp) and increased free ends (FE) were correlated with decreased JSW after accounting for BMI, gender and knee malalignment. These relationships were dependent on site of JSW measurement. CONCLUSION High reproducibility in quantifying bone sclerosis using Tb.Sp and its significant relationship with JSW demonstrated potential for assessing OA progression. Increased trabecular FE and reduced porosity observed with smaller JSW suggest collapsing subchondral bone or trabecular plate perforation in advanced knee OA.

Reproducibility of computer-assisted joint alignment measurement in OA knee radiographs

OBJECTIVES (1) To investigate the reproducibility of computer-assisted measurements of knee alignment angle (KA) from digitized radiographs of osteoarthritis (OA) participants requiring total knee arthroplasty (TKA) and (2) to determine whether landmark choice affects the precision of KA measurements on radiographs. METHODS Using a custom algorithm, femoral, central, and tibial measurement-guiding rules were interactively placed on digitized posteroanterior fixed-flexion knee radiographs by mouse control and positioned according to different anatomic landmarks. The angle subtended by lines connecting these guiding rules was measured by three readers to assess interobserver, intraobserver and experience-inexperience reproducibility. Test-retest reproducibility was evaluated with duplicate radiographs from a healthy cohort. Reproducibility was assessed using root-mean square coefficients of variation (RMSCV%). The Bland-Altman method was performed on data obtained from varying anatomic landmarks (confidence interval, CI= 95%). RESULTS From 16 healthy and 30 TKA participants, reproducibility analyses revealed a high degree of intraobserver (n=38, RMSCV=0.56%), interobserver (n=38, RMSCV=0.72%), test-retest (n=16, RMSCV=0.87%) and experience-inexperience (n=38, RMSCV=0.73%) reproducibility with variances below 1%. Varying the orientation of tibial and femoral rules according to anatomic landmarks produced a difference that exceeded an a priori limit of agreement of -1.11 degrees to +1.67 degrees. CONCLUSION Our custom-designed software provides a robust method for measuring KAs within digitized knee radiographs. Although test-retest analyses were only performed in a healthy cohort, we anticipate a similar degree of reproducibility in an OA sample. A standardized set of anatomic landmarks employed for KA measurement is recommended since arbitrary selection of landmarks resulted in imprecise KA measurement even with a computer-assisted technique.

A Trimodality Comparison of Volumetric Bone Imaging Technologies. Part I: Short-term Precision and Validity

In vivo peripheral quantitative computed tomography (pQCT) and peripheral magnetic resonance imaging (pMRI) modalities can measure apparent bone microstructure at resolutions 200 μm or higher. However, validity and in vivo test-retest reproducibility of apparent bone microstructure have yet to be determined on 1.0 T pMRI (196 μm) and pQCT (200 μm). This study examined 67 women with a mean age of 74±9 yr and body mass index of 27.65±5.74 kg/m2, demonstrating validity for trabecular separation from pMRI, cortical thickness, and bone volume fraction from pQCT images compared with high-resolution pQCT (hr-pQCT), with slopes close to unity. However, because of partial volume effects, cortical and trabecular thickness of bone derived from pMRI and pQCT images matched hr-pQCT more only when values were small. Short-term reproducibility of bone outcomes was highest for bone volume fraction (BV/TV) and densitometric variables and lowest for trabecular outcomes measuring microstructure. Measurements at the tibia for pQCT images were more precise than at the radius. In part I of this 3-part series focused on trimodality comparisons of precision and validity, it is shown that pQCT images can yield valid and reproducible apparent bone structural outcomes, but because of longer scan time and potential for more motion, the pMRI protocol examined here remains limited in achieving reliable values.

Bone lead (Pb) content at the tibia is associated with thinner distal tibia cortices and lower volumetric bone density in postmenopausal women.

Conflicting evidence suggests that bone lead or blood lead may reduce areal bone mineral density (BMD). Little is known about how lead at either compartment affects bone structure. This study examined postmenopausal women (N=38, mean age 76 ± 8, body mass index (BMI): 26.74 ± 4.26 kg/m(2)) within the Hamilton cohort of the Canadian Multicentre Osteoporosis Study (CaMos), measuring bone lead at 66% of the non-dominant leg and at the calcaneus using (109)Cadmium X-ray fluorescence. Volumetric BMD and structural parameters were obtained from peripheral quantitative computed tomography images (200 μm in-plane resolution, 2.3 ± 0.5mm slice thickness) of the same 66% site and of the distal 4% site of the tibia length. Blood lead was measured using atomic absorption spectrometry and blood-to-bone lead partition coefficients (PBB, log ratio) were computed. Multivariable linear regression examined each of bone lead at the 66% tibia, calcaneus, blood lead and PBB as related to each of volumetric BMD and structural parameters, adjusting for age and BMI, diabetes or antiresorptive therapy. Regression coefficients were reported along with 95% confidence intervals. Higher amounts of bone lead at the tibia were associated with thinner distal tibia cortices (-0.972 (-1.882, -0.061) per 100 μg Pb/g of bone mineral) and integral volumetric BMD (-3.05 (-6.05, -0.05) per μg Pb/g of bone mineral). A higher PBB was associated with larger trabecular separation (0.115 (0.053, 0.178)), lower trabecular volumetric BMD (-26.83 (-50.37, -3.29)) and trabecular number (-0.08 (-0.14, -0.02)), per 100 μg Pb/g of bone mineral after adjusting for age and BMI, and remained significant while accounting for diabetes or use of antiresorptives. Total lead exposure activities related to bone lead at the calcaneus (8.29 (0.11, 16.48)) and remained significant after age and antiresorptives-adjustment. Lead accumulated in bone can have a mild insult on bone structure; but greater partitioning of lead in blood versus bone revealed more dramatic effects on both microstructure and volumetric BMD.

A Trimodality Comparison of Volumetric Bone Imaging Technologies. Part II: 1-Yr Change, Long-Term Precision, and Least Significant Change

The previous article in this 3-part series demonstrated short-term precision and validity for volumetric bone outcome quantification using in vivo peripheral (p) quantitative computed tomography (pQCT) and magnetic resonance imaging (MRI) modalities at resolutions 200 μm or higher. However, 1-yr precision error and clinically significant references are yet to be reported for these modalities. This study examined 59 women with mean age of 75 ± 9 yr and body mass index of 26.84 ± 4.77 kg/m², demonstrating the lowest 1-yr precision error, standard errors of the estimate, and least significant change values for high-resolution (hr) pQCT followed by pQCT, and 1.0-T pMRI for all volumetric bone outcomes except trabecular number. Like short-term precision, 1-yr statistics for trabecular separation were similar across modalities. Excluding individuals with a previous history of fragility fractures, or who were current users of antiresorptives reduced 1-yr change for bone outcomes derived from pQCT and pMR images, but not hr-pQCT images. In Part II of this 3-part series focused on trimodality comparisons of 1-yr changes, hr-pQCT was recommended to be the prime candidate for quantifying change where smaller effect sizes are expected, but pQCT was identified as a feasible alternative for studies expecting larger changes.

Assessing Adherence to Teriparatide Therapy, Causes of Nonadherence and Effect of Adherence on Bone Mineral Density Measurements in Osteoporotic Patients at High Risk for Fracture

Objectives: To determine (a) adherence rates at 6, 9 and 18 months amongst patients receiving teriparatide treatment for severe osteoporosis and (b) causes of therapy discontinuation and the effect of teriparatide on bone mineral density (BMD) in adherent and nonadherent patients at different time intervals. Methods: A retrospective chart review of 111 patients receiving teriparatide from September 2004 to June 2007 was performed. Patients’ self-reports were used to record adherence and causes of nonadherence at 6, 9 and 18 months. BMDs for all patients were measured using the same DXA scanner at baseline and follow up. Results: Of 111 participants, 17 were male (mean age 60 years) and 94 were female (mean age 69 years). Of these, 12 did not initiate therapy and 4 were lost to follow up. Reported adherence was 89.6% at 6 months, 87.6% at 9 months and 74.7% at 18 months. Causes of nonadherence included cost (n = 4), no benefit (n = 1) and adverse events (n = 8). Common adverse events were leg cramps (n = 9), headache (n = 5) and myalgia (n = 4). Mean spine and femur BMD changes were 3.30% and 0.67% at 4—9 months respectively, and 5.39% and 0.77% at 10—18 months respectively. Conclusion: Adherence to teriparatide was almost 90% at 9 months and decreased to 75% at 18 months. Adverse events led to nonadherence in 20% of patients. Those who were nonadherent had lower baseline BMD values than those who were adherent. Changes in BMD at the lumbar spine were greater than changes observed at the femoral neck.

A Trimodality Comparison of Volumetric Bone Imaging Technologies. Part III: SD, SEE, LSC Association With Fragility Fractures

Part II of this 3-part series demonstrated 1-yr precision, standard error of the estimate, and 1-yr least significant change for volumetric bone outcomes determined using peripheral (p) quantitative computed tomography (QCT) and peripheral magnetic resonance imaging (pMRI) modalities in vivo. However, no clinically relevant outcomes have been linked to these measures of change. This study examined 97 women with mean age of 75 ± 9 yr and body mass index of 26.84 ± 4.77 kg/m(2), demonstrating a lack of association between fragility fractures and standard deviation, least significant change and standard error of the estimate-based unit differences in volumetric bone outcomes derived from both pMRI and pQCT. Only cortical volumetric bone mineral density and cortical thickness derived from high-resolution pQCT images were associated with an increased odds for fractures. The same measures obtained by pQCT erred toward significance. Despite the smaller 1-yr and short-term precision error for measures at the tibia vs the radius, the associations with fractures observed at the radius were larger than at the tibia for high-resolution pQCT. Unit differences in cortical thickness and cortical volumetric bone mineral density able to yield a 50% increase in odds for fractures were quantified here and suggested as a reference for future power computations.

Measuring Marrow Density and Area Using Peripheral Quantitative Computed Tomography at the Tibia: Precision in Young and Older Adults and Individuals With Spinal Cord Injury

The objective of this study was to compare the test-retest precision error for peripheral quantitative computed tomography (pQCT)-derived marrow density and marrow area segmentation at the tibia using 3 software packages. A secondary analysis of pQCT data in young adults (n = 18, mean ± standard deviation 25.4 ± 3.2 yr), older adults (n = 47, 71.8 ± 8.2 yr), and individuals with spinal cord injury (C1-T12 American Spinal Injury Association Impairment Scale, classes A-C; n = 19, 43.5 ± 8.6 yr) was conducted. Repeat scans of the tibial shaft (66%) were performed using pQCT (Stratec XCT2000). Test-retest precision errors (root mean square standard deviation and root mean square coefficient of variation [RMSCV%]) for marrow density (mg/cm3) and marrow area (mm2) were reported for the watershed-guided manual segmentation method (SliceOmatic version 4.3 [Sliceo-WS]) and the 2 threshold-based edge detection methods (Stratec version 6.0 [Stratec-TB] and BoneJ version 1.3.14 [BoneJ-TB]). Bland-Altman plots and 95% limits of agreement were computed to evaluate test-retest discrepancies within and between methods of analysis and subgroups. RMSCV% for marrow density segmentation was >5% for all methods across subgroups (Stratec-TB: 12.2%-28.5%, BoneJ-TB: 14.5%-25.2%, and Sliceo-WS: 10.9%-23.0%). RMSCV% for marrow area segmentation was within 5% for all methods across subgroups (Stratec-TB: 1.9%-4.4%, BoneJ-TB: 2.6%-5.1%, and Sliceo-WS: 2.4%-4.5%), except using BoneJ-TB in older adults. Intermethod discrepancies in marrow density appeared to be present across the range of marrow density values and did not differ by subgroup. Intermethod discrepancies varied to a greater extent for marrow area and were found to be more frequently at mid- to higher-range values for those with spinal cord injury. Precision error for pQCT-derived marrow density segmentation exceeded 5% for all methods of analysis across a range of bone mineral densities and fat infiltration, whereas precision error for marrow area segmentation ranged from 2% to 5%. Further investigation is necessary to determine alternative acquisition and analysis methods for pQCT-derived marrow segmentation.