Shoujun Zhao

Ultrasound velocity of trabecular cubes reflects mainly bone density and elasticity.

Abstract. Studies have indicated that quantitative ultrasound (QUS) variables may be influenced by the mechanical properties of bone which in turn are determined by bones material and structural properties. However, from these studies it is unclear what role density, elasticity, and structure play in determining velocity. Eighteen defatted, 12-mm cubic trabecular bone specimens were cut from cadaveric specimens. Amplitude-dependent speed of sound (SOS) using a single point QUS system was assessed in three orthogonal axes. Magnetic resonance images were obtained, from which measures of apparent trabeuclar structure were derived. The specimens were nondestructively tested in compression along three orthogonal axes defined by the sides of the cubes. The elastic modulus (in the three directions) and the strength (in one direction) were determined. Trabecular BMD was measured by quantitative computed tomography. SOS varied significantly with direction of measurement, with the highest value in the axial direction (axial:1715 m/s, sagittal: 1662 m/second, and coronal: 1676 m/s). SOS of each of the three axes was generally associated with the various mechanical (r = 0.30–0.87), density (r = 0.81–0.93), and bone structural variables (0.3–0.8). However, after adjusting the SOS correlations by density, only the correlation with elasticity remained significant in the coronal direction. BMD alone explained 88–93% of variance in SOS whereas in the multivariate model, BMD plus elasticity and/or anisotropic variables explained 96–98% of the variance in SOS. Variability of SOS is explained mostly by density and to a small extent by elasticity or anisotropy. Since only 2–6% of the variance of the QUS measurement is not explained by density and elasticity, one could conclude that the remaining variance reflects other properties of bone or perhaps simply measurement error. Evidence that these other properties may be structure related is only found in the anisotropy of QUS parameter.

Assessment of a new quantitative ultrasound calcaneus measurement: Precision and discrimination of hip fractures in elderly women compared with dual X-ray absorptiometry

Abstract: The incidence of osteoporotic hip fracture increases in postmenopausal women with low hip bone mineral density (BMD). Dual X-ray absorptiometry (DXA) is the most commonly used technique for the assessment of bone status and provides good measurement precision. However, DXA affords little information about bone architecture. Quantitative ultrasound (QUS) systems have been developed to evaluate bone status for assessment of fracture risk. Our study was designed to assess a new QUS system from Hologic, the Sahara; to compare it with a previous model, the Walker-Sonix UBA 575+; and to investigate whether it is able to discriminate between women with and without fracture. Using both ultrasound devices, the measurements were performed at the heels of 33 postmenopausal women who had recently sustained hip fracture. A control group of 35 age-matched postmenopausal women was recruited for comparison. The total, neck and trochanter femoral BMD values were assessed using DXA for both groups. QUS and DXA measurements were significantly lower in fractured patients (p<0.005) than in the control group. The short-term, mid-term and standardized short-term precisions were used to evaluate the reproducibility of the two QUS systems. The Sahara showed a better standardized coefficient of variation for broadband ultrasound attenuation (BUA) than did the UBA 575+ (p<0.001). The correlation of BUA and speed of sound (SOS) between the two QUS devices was highly significant, with an r value of 0.92 for BUA and 0.91 for SOS. However, the correlation between DXA and ultrasound parameters ranged from 0.28 to 0.44. We found that ultrasound measurements at the heel were significant discriminators of hip fractures with odds ratios (OR) ranging from 2.7 to 3.2. Even after adjusting the logistic regressions for total, neck or trochanter femoral BMD, QUS variables were still significant independent discriminators of hip fracture. The areas under the ROC curves of each ultrasound parameter ranged from 0.75 to 0.78, and compared very well with femoral neck BMD (p>0.05). In conclusion, our study indicated that the calcaneal QUS variables, as measured by the Sahara system can discriminate hip fracture patients equally as well as hip DXA.

The feasibility of characterizing the spatial distribution of cartilage T2 using texture analysis

OBJECTIVE The purpose of this study was (1) to characterize the spatial distribution of cartilage T(2) in postmenopausal osteoarthritis (OA) patients and age-matched healthy subjects using second order texture measures at baseline, and (2) to analyze changes in the texture of cartilage T(2) after 9 months. METHODS 3.0T-MRI of the knee was performed in 8 mild OA patients and 10 age-matched controls at baseline and after 9 months. Cartilage T(2), volume, and average thickness were calculated in all patients. Texture analysis, based on the gray level co-occurrence matrix, was performed on the cartilage T(2) maps. Texture parameters, including entropy and angular second moment, were calculated at 0 degrees (corresponding to the anterior-posterior axis) and at 90 degrees (corresponding to the superior-inferior axis), with pixel offsets ranging from 1 to 3 pixels. RESULTS Least square means analysis showed that mean T(2) values, their standard deviation (SD), and their entropy were greater (P<0.05) in OA patients than in controls. Over 9 months, the SD and entropy of cartilage T(2) significantly (P<0.05) decreased in OA patients, while no significant changes were evident in cartilage thickness or volume. CONCLUSION The mean cartilage T(2) values, their SD, and their entropy were greater in OA patients than in controls, indicating that the T(2) values in osteoarthritic cartilage are not only elevated, but also more heterogeneous than those in healthy cartilage. The longitudinal results demonstrate that changes in texture parameters of cartilage T(2) may precede morphological changes in thickness and volume in the progression of OA.

PRETREATMENT ENDORECTAL MAGNETIC RESONANCE IMAGING AND MAGNETIC RESONANCE SPECTROSCOPIC IMAGING FEATURES OF PROSTATE CANCER AS PREDICTORS OF RESPONSE TO EXTERNAL BEAM RADIOTHERAPY

PURPOSE To evaluate whether pretreatment combined endorectal magnetic resonance imaging (MRI) and magnetic resonance spectroscopic imaging (MRSI) findings are predictive of outcome in patients who undergo external beam radiotherapy for prostate cancer. METHODS AND MATERIALS We retrospectively identified 67 men with biopsy-proven prostate cancer who underwent combined endorectal MRI and MRSI at our institution between January 1998 and October 2003 before whole-pelvis external beam radiotherapy. A single reader recorded tumor presence, stage, and metabolic abnormality at combined MRI and MRSI. Kaplan-Meier survival and Cox univariate and multivariate analyses explored the relationship between clinical and imaging variables and outcome, using biochemical or metastatic failure as endpoints. RESULTS After a mean follow-up of 44 months (range, 3-96), 6 patients developed both metastatic and biochemical failure, with an additional 13 patients developing biochemical failure alone. Multivariate Cox analysis demonstrated that the only independent predictor of biochemical failure was the volume of malignant metabolism on MRSI (hazard ratio [HR] 1.63, 95% confidence interval [CI] 1.29-2.06; p < 0.0001). The two independent predictors of metastatic failure were MRI tumor size (HR 1.34, 95% CI 1.03-1.73; p = 0.028) and the finding of seminal vesicle invasion on MRI (HR 28.05, 95% CI 3.96-198.67; p = 0.0008). CONCLUSIONS In multivariate analysis, MRI and MRSI findings before EBRT in patients with prostate cancer are more accurate independent predictors of outcome than clinical variables, and in particular, the findings of seminal vesicle invasion and extensive tumor predict a worse prognosis.

Prostate Cancer: Is Inapparent Tumor at Endorectal MR and MR Spectroscopic Imaging a Favorable Prognostic Finding in Patients Who Select Active Surveillance?

PURPOSE To retrospectively determine whether inapparent tumor at endorectal magnetic resonance (MR) imaging and MR spectroscopic imaging is a favorable prognostic finding in prostate cancer patients who select active surveillance for management. MATERIALS AND METHODS Committee on Human Research approval was obtained and compliance with HIPAA regulations was observed, with waiver of requirement for written consent. Ninety-two men (mean age, 64 years; range, 43-85 years) were retrospectively identified who had biopsy-proved prostate cancer, who had undergone baseline endorectal MR imaging and MR spectroscopic imaging, and who had selected active surveillance for management. Their mean baseline serum prostate-specific antigen (PSA) level was 5.5 ng/mL, and the median Gleason score was 6. Two readers with 10 and 3 years of experience independently reviewed all MR images and determined whether tumor was apparent on the basis of evaluation of established morphologic and metabolic findings. Another investigator compiled data about baseline clinical stage, biopsy findings, and serum PSA measurements. Multiple logistic regression analysis was used to investigate the relationship between the clinical parameters and tumor apparency at MR imaging and the biochemical outcome. RESULTS At baseline MR imaging, readers 1 and 2 considered 54 and 26 patients, respectively, to have inapparent tumor (fair interobserver agreement; kappa = 0.30). During a mean follow-up of 4.8 years, 52 patients had a stable PSA level and 40 had an increasing PSA level. In multivariate analysis, no significant association was found between the baseline clinical stage, Gleason score, serum PSA level, or the presence of apparent tumor at endorectal MR imaging and MR spectroscopic imaging for either reader and the biochemical outcome (P > .05 for all). CONCLUSION Endorectal MR imaging and MR spectroscopic imaging findings of tumor apparency or inapparency in prostate cancer patients who select active surveillance for management do not appear to be of prognostic value.

Prostate Cancer: Role of Pretreatment MR in Predicting Outcome after External-Beam Radiation Therapy—Initial Experience

PURPOSE To retrospectively determine if pretreatment endorectal magnetic resonance (MR) imaging findings are predictive of outcome in patients who undergo external-beam radiation therapy for prostate cancer. MATERIALS AND METHODS Committee on Human Research approval, with waiver of the requirement for informed consent, was obtained for this HIPAA-compliant study. Eighty men with biopsy-proved prostate cancer (mean age, 59 years; range, 47-75 years) who underwent endorectal MR imaging of the prostate prior to external-beam radiation therapy were retrospectively identified; details of baseline tumor characteristics, treatment, and outcome were recorded. Two experienced readers independently reviewed all MR imaging studies and recorded tumor T stage and the radial diameter of extracapsular extension (if present). Univariate and multivariate stepwise Cox regression analyses were used to investigate the relationship between baseline imaging and clinical predictive variables and the end point of metastatic failure. RESULTS At MR imaging, readers 1 and 2, respectively, considered 50 and 60 patients to have T1 or T2 disease (ie, organ-confined disease) and 30 and 20 patients to have T3 disease. After a mean follow-up of 43 months, four patients developed metastases. Univariate Cox analysis revealed that baseline serum prostate-specific antigen level, presence of extracapsular extension at MR imaging (according to either reader), and degree of extracapsular extension (according to either reader) were all significantly (P < .05) related to the development of metastases. Multivariate Cox analysis revealed that the sole independent predictive variable was mean diameter of extracapsular extension (relative hazard ratio, 2.06; 95% confidence interval: 1.22, 3.48; P = .007). In particular, three of five patients with extracapsular extension of more than 5 mm at pretreatment MR imaging developed metastases 24, 43, and 63 months after therapy. CONCLUSION The presence and degree of extracapsular extension at MR imaging prior to external-beam radiation therapy are important predictors of posttreatment metastatic recurrence.

In Vivo Magnetic Resonance Imaging and Optical Imaging Comparison of Viable and Nonviable Mesenchymal Stem Cells with a Bifunctional Label

The purpose of this study was to compare viable and nonviable bilabeled mesenchymal stem cells (MSCs) in arthritic joints with magnetic resonance imaging (MRI) and optical imaging (OI). MSCs were labeled with ferucarbotran and DiD. MRI and OI of bilabeled cells were compared with controls. Six rats with arthritis received intra-articular injections of bilabeled viable MSCs into the right knee and nonviable MSCs into the left knee. Animals underwent MRI and OI preinjection and at 4, 24, 48, and 72 hours postinjection. The results were analyzed with a mixed random effects model and Fisher probability. Bilabeled MSCs showed increased MRI and OI signals compared to unlabeled controls (p < .0001). After intra-articular injection, bilabeled MSCs caused significant T2 and T2* effect on MRI and fluorescence on OI up to 72 hours postinjection (p < .05). There was no significant difference between viable and nonviable MSC signal in the knee joints; however, some of the viable cells migrated to an adjacent inflamed ankle joint (p < .05). Immunohistochemistry confirmed viable MSCs in right knee and ankle joints and nonviable MSCs in the left knee. Viable and nonviable cells could not be differentiated with MRI or OI signal intensity but were differentiated based on their ability to migrate in vivo.

T2-weighted endorectal magnetic resonance imaging of prostate cancer after external beam radiation therapy

PURPOSE To retrospectively determine the accuracy of T2-weighted endorectal MR imaging in the detection of prostate cancer after external beam radiation therapy and to investigate the relationship between imaging accuracy and time since therapy. MATERIALS AND METHODS Institutional review board approval was obtained and the study was HIPPA compliant. We identified 59 patients who underwent 1.5 Tesla endorectal MR imaging of the prostate between 1999 and 2006 after definitive external beam radiation therapy for biopsy-proven prostate cancer. Two readers recorded the presence or absence of tumor on T2-weighted images. Logistic regression and Fishers exact tests for 2x2 tables were used to determine the accuracy of imaging and investigate if accuracy differed between those imaged within 3 years of therapy (n = 25) and those imaged more than 3 years after therapy (n = 34). Transrectal biopsy was used as the standard of reference for the presence or absence of recurrent cancer. RESULTS Thirty-four of 59 patients (58%) had recurrent prostate cancer detected on biopsy. The overall accuracy of T2-weighted MR imaging in the detection cancer after external beam radiation therapy was 63% (37/59) for reader 1 and 71% for reader 2 (42/59). For both readers, logistic regression showed no difference in accuracy between those imaged within 3 years of therapy and those imaged more than 3 years after therapy (p = 0.86 for reader 1 and 0.44 for reader 2). CONCLUSION T2-weighted endorectal MR imaging has low accuracy in the detection of prostate cancer after external beam radiation therapy, irrespective of the time since therapy.

Impact of Age on Quality-of-life Outcomes After Treatment for Localized Prostate Cancer

BACKGROUND Men aged >65 yr are less likely to receive local therapy for prostate cancer (PCa), perhaps because of concerns about quality-of-life (QOL) outcomes. OBJECTIVE To describe QOL before and after PCa treatment in men of varying ages. DESIGN, SETTING, AND PARTICIPANTS Participants enrolled in CaPSURE who underwent radical prostatectomy, brachytherapy, external beam radiation, androgen deprivation therapy, or active surveillance for localized PCa. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS QOL changes over time were assessed among age groups using repeated-measures mixed models adjusted for race, year, clinical risk, treatment, comorbidities, and an age-time interaction term. Differences are reported as adjusted least-square means and percentage decline. Secondary analyses evaluated age and QOL for local (prostatectomy, radiation) compared to nonlocal treatment (hormonal, surveillance). RESULTS AND LIMITATIONS Older men had lower mean unadjusted pre- and post-treatment QOL scores for nearly all domains. Of the domains evaluated, adjusted mean sexual function, sexual bother, and urinary function showed greater declines from baseline to 2 yr. At 2 yr, more men <60 yr than those >70 yr experienced declines in urinary function (14% vs 9%) and sexual bother (39% vs 17%). Declines in these domains were also greater for local than for nonlocal treatment. CONCLUSIONS Definitive treatment for localized disease should not be deferred for older men because of fears regarding QOL declines. Younger men should be counseled about potential post-treatment declines in QOL despite higher absolute QOL scores. Communicating these differences to patients will facilitate more appropriate treatment decision-making in men of all ages. PATIENT SUMMARY In this study we evaluated quality of life before and after treatment for localized prostate cancer in a diverse patient population. Declines in quality of life after treatment varied according to age and treatment. We conclude that counseling about quality of life will help patients of all ages to make more appropriate treatment decisions.

Labeling human embryonic stem cell-derived cardiomyocytes with indocyanine green for noninvasive tracking with optical imaging: an FDA-compatible alternative to firefly luciferase.

Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) have demonstrated the ability to improve myocardial function following transplantation into an ischemic heart; however, the functional benefits are transient possibly due to poor cell retention. A diagnostic technique that could visualize transplanted hESC-CMs could help to optimize stem cell delivery techniques. Thus, the purpose of this study was to develop a labeling technique for hESCs and hESC-CMs with the FDA-approved contrast agent indocyanine green (ICG) for optical imaging (OI). hESCs were labeled with 0.5, 1.0, 2.0, and 2.5 mg/ml of ICG for 30, 45, and 60 min at 37 degrees C. Longitudinal OI studies were performed with both hESCs and hESC-CMs. The expression of surface proteins was assessed with immunofluorescent staining. hESCs labeled with 2 mg ICG/ml for 60 min achieved maximum fluorescence. Longitudinal studies revealed that the fluorescent signal was equivalent to controls at 120 h postlabeling. The fluorescence signal of hESCs and hESC-CMs at 1, 24, and 48 h was significantly higher compared to precontrast data (p < 0.05). Immunocytochemistry revealed retention of cell-specific surface and nuclear markers postlabeling. These data demonstrate that hESCs and hESC-CMs labeled with ICG show a significant fluorescence up to 48 h and can be visualized with OI. The labeling procedure does not impair the viability or functional integrity of the cells. The technique may be useful for assessing different delivery routes in order to improve the engraftment of transplanted hESC-CMs or other stem cell progenitors.