AAV2-VEGF-B gene therapy failed to induce angiogenesis in ischemic porcine myocardium due to inflammatory responses.

Therapeutic angiogenesis induced by gene therapy is a promising approach to treat patients suffering from severe coronary artery disease. In small experimental animals, adeno-associated viruses (AAVs) have shown good transduction efficacy and long-term transgene expression in heart muscle and other tissues. However, it has been difficult to achieve cardiac-specific angiogenic effects with AAV vectors. We tested the hypothesis whether AAV2 gene transfer (1 × 1013 vg) of vascular endothelial growth factor B (VEGF-B186) together with immunosuppressive corticosteroid treatment can induce long-term cardiac-specific therapeutic effects in the porcine ischemic heart. Gene transfers were delivered percutaneously using direct intramyocardial injections, improving targeting and avoiding direct contact with blood, thus reducing the likelihood of immediate immune reactions. After 1- and 6-month time points, the capillary area was analyzed, myocardial perfusion reserve (MPR) was measured with radiowater positron emission tomography ([15O]H2O-PET), and fluorodeoxyglucose ([18F]FDG) uptake was used to evaluate myocardial viability. Clinical chemistry and immune responses were analyzed using standard methods. After 1- and 6-month follow-up, AAV2-VEGF-B186 gene transfer failed to induce angiogenesis and improve myocardial perfusion and viability. Here, we show that inflammatory responses attenuated the therapeutic effect of AAV2 gene transfer by significantly reducing successful transduction and long-term gene expression despite the efforts to reduce the likelihood of immune reactions and the use of targeted local gene transfer methods.

Respiratory motion reduction with a dual gating approach in myocardial perfusion SPECT: Effect on left ventricular functional parameters.

BACKGROUND: Respiratory motion (RM) complicates the analysis of myocardial perfusion (MP) single-photon emission computed tomography (SPECT) images. The effects of RM on left ventricular (LV) functional variables have not been thoroughly investigated. METHODS AND RESULTS: Thoracic electrical bioimpedance and electrocardiographic signals were recorded from eighteen patients undergoing the rest phase of a 1-day stress/rest cardiac-gated MP-SPECT examination. The signals and list-mode emission data were retrospectively processed to yield standard cardiac- and dual-gated (respiratory and cardiac gating) image sets applying a novel algorithm. LV volume, MP, shape index (SI), wall motion (WM), wall thickening (WT), and phase analysis parameters were measured with Quantitative Perfusion SPECT/Quantitative Gated SPECT software (Cedars-Sinai Medical Center). Image quality was evaluated by three experienced physicians. Dual gating increased LV volume (77.1 ± 26.8 vs 79.8 ± 27.6 mL, P = .006) and decreased SI (0.57 ± 0.05 vs 0.56 ± 0.05, P = .036) and global WT (39.0 ± 11.8% vs 36.9 ± 9.4%, P = .034) compared to cardiac gating, but did not significantly alter perfusion, WM or phase analysis parameters or image quality (P > .05). CONCLUSIONS: RM reduction has an effect on LV volume, shape, and WT parameters. RM exerts no significant effect on phase analysis parameters.

Dependence of left ventricular functional parameters on image acquisition time in cardiac-gated myocardial perfusion SPECT.

BACKGROUND: Reduction of image acquisition time in single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) examinations has been considered. However, association between left ventricular (LV) functional parameters and acquisition time is unclear. METHODS: Twenty-four patients referred to one-day stress/rest SPECT MPI examinations were imaged at rest with dual-headed gamma camera. List-mode emission data were processed into sets of cardiac-gated images corresponding to different acquisition times: 20%, 30%, 40%, 50%, 60%, 80%, and 100% of total acquisition time (30 seconds per projection). Image quality was quantitatively evaluated by computing contrast-to-noise ratio. LV volumes, wall motion, wall thickening, and mechanical dyssynchrony were quantified with automatic clinical software (QGS; Cedars-Sinai Medical Center). RESULTS: A significant negative dependence was found between phase analysis parameter values and image acquisition time. Differences in LV volume parameters were small but statistically significant at relative acquisition times of less than 50%. LV wall motion and wall thickening were found to be robust to the increase of noise. CONCLUSIONS: Image acquisition time of gated SPECT MPI examination can be reduced to 15 seconds per projection without significantly affecting LV volumes, wall motion, or wall thickening. However, reduction of acquisition time has a significant effect on phase analysis results.

Cardiorespiratory fitness, respiratory function and hemodynamic responses to maximal cycle ergometer exercise test in girls and boys aged 9-11 years: the PANIC Study.

PURPOSE: We aimed to provide comprehensive data on and reference values for cardiorespiratory fitness, respiratory function and hemodynamic responses during and after maximal cycle ergometer test in children. METHODS: The participants were a population sample of 140 children (69 girls) aged 9-11 years. Heart rate (HR) and systolic blood pressure (SBP) were measured from pre-exercise rest to the end of recovery. Respiratory gases were measured directly by the breath-by-breath method. Peak workload, HR changes, peak oxygen uptake (VO2), peak oxygen pulse (O2 pulse), peak respiratory exchange ratio (RER) and the lowest ratio of ventilation and carbon dioxide output (VE/VCO2) during the exercise test in girls and boys were presented according to their distributions in 5 categories. RESULTS: HR decreased more during 4-min recovery in boys than in girls (76 vs. 67 beats/min, p < 0.001), whereas SBP decrease was similar in boys and girls (30 vs. 22 mmHg, p = 0.66). Boys had a higher peak VO2 per weight [51.9 vs. 47.6 ml/kg/min, p < 0.001] and per lean mass [67.3 vs. 63.0 ml/kg/min, p < 0.001] than girls. Peak O2 pulse per lean mass was higher in boys than in girls (0.34 vs. 0.31 ml/kg/beat, p < 0.001). There was no difference in the lowest VE/VCO2 during the test between boys and girls (28 vs. 29, p = 0.18). CONCLUSIONS: The indicators of cardiorespiratory fitness were better in boys than in girls. These data enable the evaluation of cardiorespiratory function during and after maximal exercise test and the detection of children with abnormal values.

Influence of different DXA acquisition modes on monitoring the changes in bone mineral density after hip resurfacing arthroplasty.

Dual-energy X-ray absorptiometry (DXA) is a technique enabling the measurement of bone mineral density (BMD) around prostheses after hip resurfacing arthroplasty (HRA). In this study, we evaluated the consistency of different DXA acquisition modes with 33 patients who had undergone HRA. Patients were scanned with DXA immediately after surgery and at 3-, 6-, and 12-mo time points. All the patients were scanned with dual femur and orthopedic hip acquisition modes and analyzed using 10-region ROI model. With both acquisition modes, a statistically significant decrease (p<0.05, Wilcoxon's test) in BMD at 3mo was revealed in 3 ROIs, located to upper and lateral upper femur. Both acquisition modes detected similarly (p<0.01) preservation of the femoral bone stock within 12mo in all but 1 ROI. The applied acquisition protocols involved the use of different footplates for hip fixation. Because the differences between acquisition modes ranged between +1.6% and -7.1% and the reproducibility of BMD values can vary by as much as 28% due to hip rotation, it is proposed that both dual femur and orthopedic hip acquisition modes can be used to monitor the changes in BMD after HRA. However, the same hip rotation is recommended for all DXA measurements.

Bone mineral density of the proximal femur after hip resurfacing arthroplasty: 1-year follow-up study.

BACKGROUND: Hip resurfacing arthroplasty (HRA) is considered a bone-preserving procedure and may eliminate proximal femoral stress shielding and osteolysis. However, in addition to implant-related stress-shielding factors, various patient-related factors may also have an effect on bone mineral density (BMD) of the proximal femur in patients with HRA. Thus, we studied the effects of stem-neck angle, demographic variables, and physical functioning on the BMD of the proximal femur in a one-year follow-up. METHODS: Thirty three patients (9 females and 24 males) with a mean (SD) age of 55 (9) years were included in the study. BMD was measured two days and 3, 6, and 12 months postoperatively and 10 regions of interest (ROI) were used. Stem-neck angle was analyzed from anteroposterior radiographs. RESULTS: Three months postoperatively, BMD decreased in six out of 10 regions of interest (ROI) on the side operated on and in one ROI on the control side (p<0.05) compared to the second postoperative day. At 12 months, BMD had increased in 7 ROIs on the operated side and one ROI on the control side (all p<0.001). Correlation was found between the stem-neck angle and BMD in ROIs 2, 3, 7, and 9 (r=0.36-0.61). In multiple regression analysis, stem-neck angle, age, sex, body mass index, and walking distance did not explain the BMD changes. CONCLUSIONS: After an early drop, the BMD of the upper femur was restored and even exceeded the preoperative level at one year follow-up. From a clinical standpoint, the changes in BMD in these HRA patients could not be explained by stem-neck angle or patient related factors.

Effect of data conserving respiratory motion compensation on left ventricular functional parameters assessed in gated myocardial perfusion SPECT.

BACKGROUND: Respiratory motion compromises image quality in myocardial perfusion (MP) single-photon emission computed tomography (SPECT) imaging and may affect analysis of left ventricular (LV) functional parameters, including phase analysis-quantified mechanical dyssynchrony parameters. In this paper, we investigate the performance of two algorithms, respiratory blur modeling (RBM) and joint motion-compensated (JMC) ordered-subsets expectation maximization (OSEM), and the effects of motion compensation on cardiac-gated MP-SPECT studies. METHODS: Image acquisitions were carried out with a dual-detector SPECT/CT system in list-mode format. A cardiac phantom was imaged as stationary and under respiratory motion. The images were reconstructed with OSEM, RBM-OSEM, and JMC-OSEM algorithms, and compared in terms of mean squared error (MSE). Subsequently, MP-SPECT data of 19 patients were binned into dual-gated (respiratory and cardiac gating) projection images. The images of the patients were analyzed with Quantitative Gated SPECT (QGS) 2012 program (Cedars-Sinai Medical Center, USA). The parameters of interest were LV volumes, ejection fraction, wall motion, wall thickening, phase analysis, and perfusion parameters. RESULTS: In phantom experiment, compared to the stationary OSEM reconstruction, the MSE values for OSEM, RBM-OSEM, and JMC-OSEM were 8.5406·10-5,2.7190·10-5, and 2.0795·10-5, respectively. In the analysis of LV function, use of JMC had a small but statistically significant (p < 0.05) effect on several parameters: it increased LV volumes and standard deviation of phase angle histogram, and it decreased ejection fraction, global wall motion, and lateral, septal, and apical perfusion. CONCLUSIONS: Compared to standard OSEM algorithm, RBM-OSEM and JMC-OSEM both improve image quality under motion. Motion compensation has a minor effect on LV functional parameters.

Ex Vivo Porcine Models Are Valid for Testing and Training Microsurgical Lumbar Decompression Techniques.

BACKGROUND: Spinal surgeries are the leading causes for patient settlement issues. Recent European Medical Device Regulations aims to reduce complications by enforcing that surgical tools are validated before clinical use. Human cadavers are favored in preclinical use, but due to anatomic variance, decay, and scarce supply, alternative synthetic and animal models are used. This study evaluates the fidelity and validity of porcine models in training and assessment of microsurgical decompressive techniques in the lumbar spine. METHODS: Anatomic dimensions of 10 human and 5 young pig spines were assessed from computed tomography images. Novel "en bloc" fresh-frozen ex vivo porcine model tissues' fidelity and validity for decompressive surgery was evaluated by 3 expert neurosurgeons, in comparison with other models. RESULTS: The pigs' anatomic dimensions were on average 11% smaller than in humans. The pigs' L4-L5 was most alike humans, and the highest similarity was in lamina and spinous process widths, and the skin to posterior longitudinal ligament distance. Dimensional variability was higher in humans (F = 19.06-0.56, P < 0.05). The pigs' tissues were felt as good as living patients and better than cadavers for skin, fascia, bone, facets, ligamentum flavum, and dura, but poor for vessels (experts' intraclass correlation coefficient = 0.696-0.903). The pig models' validity for assessing drills' adverse features (friction, jitter, heating, and soft tissue trauma) was reported to be unanimously excellent. CONCLUSION: Pigs are representative for assessing microsurgical decompression techniques in the lower lumbar spine. The novel "en bloc" pig model can be an asset for industries and clinicians during assessment and training of new spinal techniques.

Adenoviral VEGF-B186R127S gene transfer induces angiogenesis and improves perfusion in ischemic heart.

Vascular endothelial growth factor B (VEGF-B) is an interesting therapeutic candidate for coronary artery disease. However, it can also cause ventricular arrhythmias, potentially preventing its use in clinics. We cloned VEGF-B isoforms with different receptor binding profiles to clarify the roles of VEGFR-1 and Nrp-1 in angiogenesis and to see if angiogenic properties can be maintained while avoiding side effects. VEGF-B constructs were studied in vivo using adenovirus (Ad)-mediated intramyocardial gene transfers into the normoxic and ischemic porcine heart (n = 51). It was found that the unprocessed isoform VEGF-B186R127S is as efficient angiogenic growth factor as the native VEGF-B186 in normoxic and ischemic heart. In addition, AdVEGF-B186R127S increased myocardial perfusion reserve by 22% in ischemic heart without any side effects. AdVEGF-B127 (VEGFR-1 and Nrp-1 ligand) and AdVEGF-B109 (VEGFR-1 ligand) did not induce angiogenesis. Thus, VEGF-B186 is angiogenic only before its proteolytic processing to VEGF-B127. Only the VEGF-B186 C-terminal fragment was associated with arrhythmias.

Severe Obstructive Sleep Apnea and Increased Cortical Amyloid-ß Deposition.

BACKGROUND: The suggested association between severe obstructive sleep apnea (OSA) and risk of Alzheimer's disease (AD) needs further study. Only few recent reports exist on associations between brain amyloid-ß (Aß) burden and severe OSA in middle-aged patients. OBJECTIVE: Examine the possible presence of cortical Aß accumulation in middle-aged patients with severe OSA. METHODS: We performed detailed multimodal neuroimaging in 19 cognitive intact patients (mean 44.2 years) with severe OSA (Apnea-Hypopnea Index >30 h-1). Known etiological factors for possible Aß accumulation were used as exclusion criteria. Aß uptake was studied with [11C]-PiB-PET, glucose metabolism with [18F]-FDG-PET, and structural imaging with 3.0T MRI. RESULTS: When analyzed individually, in [11C]-PiB-PET a substantial number (∼32%) of the patients exhibited statistically significant evidence of increased cortical Aß uptake based on elevated regional Z-score values, mostly seen bilaterally in the precuneus and posterior cingulum regions. Cortical glucose hypometabolism in [18F]-FDG-PET was seen in two patients. MRI did not show structural changes suggestive of AD-related pathology. CONCLUSION: Increased [11C]-PiB uptake was seen in middle-aged cognitively intact patients with severe OSA. These findings are similar to those described in cognitive unimpaired older OSA patients. The changes in cortical Aß uptake suggest that severe OSA itself may predispose to alterations related to AD already in middle-age. Aß clearance may be compromised without simultaneous evidence of metabolic or structural alterations. The results emphasize the importance of early diagnostics and proper treatment of severe OSA in cognitively intact middle-aged subjects, possibly diminishing the individual risk for later cognitive dysfunction.

Quantification of bone density of the proximal femur after hip resurfacing arthroplasty--comparison of different DXA acquisition modes.

Total hip arthroplasty (THA) is a traditional operative procedure in the treatment of osteoarthritis. The hip resurfacing arthroplasty (HRA) provides an alternative to the THA for young active patients. HRA is a bone-preserving procedure eliminating the problem of proximal femoral stress shielding and osteolysis associated to THA. Unfortunately, there is no standardized methodology to monitor the quality of bone after HRA. In this study, areal bone mineral density (BMD) in the operated hip (10 regions of interests [ROIs] of 34 volunteered HRA patients) was measured using Lunar Prodigy dual-energy X-ray absorptiometry, and the agreement of a standard (dual femur) and an orthopedic (orthopedic hip) acquisition modes was compared. Furthermore, reproducibility of the patient-specific analysis procedures was tested. The analysis procedures were reproducible with both acquisition modes (1.18%-1.37%). The mean (± standard deviation) difference between the acquisition modes was 1.46 ± 0.93%. At ROIs, a strong linear relationship was found between the results from 2 acquisition modes (R(2)=0.801-0.966, p<0.01). In conclusion, both acquisition modes were reproducible, and it is suggested that the error induced by the different acquisition modes does not affect interpretation of BMD changes after HRA surgery.

Time-modified OSEM algorithm for more robust assessment of left ventricular dyssynchrony with phase analysis in ECG-gated myocardial perfusion SPECT.

BACKGROUND: In ordered subsets expectation maximization (OSEM) reconstruction of electrocardiography (ECG)-gated myocardial perfusion single-photon emission computed tomography (SPECT), it is often assumed that the image acquisition time is constant for each projection angle and ECG bin. Due to heart rate variability (HRV), this assumption may lead to errors in quantification of left ventricular mechanical dyssynchrony with phase analysis. We hypothesize that a time-modified OSEM (TOSEM) algorithm provides more robust results. METHODS: List-mode data of 44 patients were acquired with a dual-detector SPECT/CT system and binned to eight ECG bins. First, activity ratio (AR)-the ratio of total activity in the last OSEM-reconstructed ECG bin and first five ECG bins-was computed, as well as standard deviation SDR-R of the accepted R-R intervals; their association was evaluated with Pearson correlation analysis. Subsequently, patients whose AR was higher than 90% were selected, and their list-mode data were rebinned by omitting a part of the acquired counts to yield AR values of 90%, 80%, 70%, 60% and 50%. These data sets were reconstructed with OSEM and TOSEM algorithms, and phase analysis was performed. Reliability of both algorithms was assessed by computing concordance correlation coefficients (CCCs) between the 90% data and data corresponding to lower AR values. Finally, phase analysis results assessed from OSEM- and TOSEM-reconstructed images were compared. RESULTS: A strong negative correlation (r = -0.749) was found between SDR-R and AR. As AR decreased, phase analysis parameters obtained from OSEM images decreased significantly. On the contrary, reduction of AR had no significant effect on phase analysis parameters obtained from TOSEM images (CCC > 0.88). The magnitude of difference between OSEM and TOSEM results increased as AR decreased. CONCLUSIONS: TOSEM algorithm minimizes the HRV-related error and can be used to provide more robust phase analysis results.

Effect of respiratory motion on cardiac defect contrast in myocardial perfusion SPECT: a physical phantom study.

OBJECTIVE: Correction for respiratory motion in myocardial perfusion imaging requires sorting of emission data into respiratory windows where the intra-window motion is assumed to be negligible. However, it is unclear how much intra-window motion is acceptable. The aim of this study was to determine an optimal value of intra-window residual motion. METHODS: A custom-designed cardiac phantom was created and imaged with a standard dual-detector SPECT/CT system using Tc-99m as the radionuclide. Projection images were generated from the list-mode data simulating respiratory motion blur of several magnitudes from 0 (stationary phantom) to 20 mm. Cardiac defect contrasts in six anatomically different locations, as well as myocardial perfusion of apex, anterior, inferior, septal and lateral walls, were measured at each motion magnitude. Stationary phantom data were compared to motion-blurred data. Two physicians viewed the images and evaluated differences in cardiac defect visibility and myocardial perfusion. RESULTS: Significant associations were observed between myocardial perfusion in the anterior and inferior walls and respiratory motion. Defect contrasts were found to decline as a function of motion, but the magnitude of the decline depended on the location and shape of the defect. Defects located near the cardiac apex lost contrast more rapidly than those located on the anterior, inferior, septal and lateral wall. The contrast decreased by less than 5% at every location when the motion magnitude was 2 mm or less. According to a visual evaluation, there were differences in myocardial perfusion if the magnitude of the motion was greater than 1 mm, and there were differences in the visibility of the cardiac defect if the magnitude of the motion was greater than 9 mm. CONCLUSIONS: Intra-window respiratory motion should be limited to 2 mm to effectively correct for respiratory motion blur in myocardial perfusion SPECT.

Ultrasonic characterization of human trabecular bone microstructure.

New quantitative ultrasound (QUS) techniques involving ultrasound backscattering have been introduced for the assessment of bone quality. QUS parameters are affected by the transducer characteristics, e.g. frequency range, wave and pulse length. Although frequency-dependent backscattering has been studied extensively, understanding of the ultrasound scattering phenomenon in trabecular bone is still limited. In the present study, the relationships between QUS parameters and the microstructure of human trabecular bone were investigated experimentally and by using numerical simulations. Speed of sound (SOS), normalized broadband ultrasound attenuation (nBUA), average attenuation, integrated reflection coefficient (IRC) and broadband ultrasound backscatter (BUB) were measured for 26 human trabecular bone cylinders. Subsequently, a high-resolution microCT system was used to determine the microstructural parameters. Moreover, based on the sample-specific microCT data, a numerical model for ultrasound propagation was developed for the simulation of experimental measurements. Experimentally, significant relationships between the QUS parameters and microstructural parameters were demonstrated. The relationships were dependent on the frequency, and the strongest association (r = 0.88) between SOS and structural parameters was observed at a centre frequency of 5 MHz. nBUA, average attenuation, IRC and BUB showed somewhat lower linear correlations with the structural properties at a centre frequency of 5 MHz, as compared to those determined at lower frequencies. Multiple regression analyses revealed that the variation of acoustic parameters could best be explained by parameters reflecting the amount of mineralized tissue. A principal component analysis demonstrated that the strongest determinants of BUB and IRC were related to the trabecular structure. However, other structural characteristics contributed significantly to the prediction of the acoustic parameters as well. The two-dimensional numerical model introduced in the present study demonstrated good agreement with the experimental measurements. However, further studies with the simulation model are warranted to systematically investigate the relation between the structural parameters and ultrasound scattering.

Influence of overlying soft tissues on trabecular bone acoustic measurement at various ultrasound frequencies.

Ultrasound (US) has been introduced as a promising tool for osteoporosis diagnostics. However, soft tissues overlying the bones affect reliability of the ultrasound (US) techniques. In this in vitro study, the effect of soft tissues on bone US measurements was investigated numerically and experimentally. Particularly, the dependence of the error induced by soft tissues on the applied US frequency (0.3 to 6.7 MHz) was addressed. For these aims, human trabecular bone samples (n = 25) were measured using acoustic, dual energy x-ray absorptiometry (DXA) and mechanical techniques. US attenuation, speed, reflection and backscattering were determined from the through-transmission and pulse-echo measurements. Numerical correction, based on the inclusion of acoustic characteristics of specific soft tissue components, i.e., adipose and lean tissues, was derived for the analysis of experimental measurements. Values of US parameters, interrelationships between the US parameters and mechanical properties, as well as the errors induced by the soft tissues, were significantly dependent on the US frequency. The errors induced by the soft tissues on the US measurement were typically reduced by approximately 50% after introduction of the numerical correction technique. Thereby, the acoustic prediction of mechanical properties of trabecular bone was also improved. We conclude that the numerical correction of the contribution of overlying soft tissues on acoustic measurements can reduce uncertainties related to in vivo US measurements.

BMI influence on the reproducibility of ECG-gated myocardial perfusion imaging phase analysis in comparison with novel echocardiographic dyssynchrony estimation methods.

AIM: Cardiac resynchronization therapy (CRT) is a treatment for patients with end-stage heart failure. However, two-thirds of the patients are nonresponders. Evaluation of left ventricular mechanical dyssynchrony may help in finding patients who will benefit from CRT. Dyssynchrony can be evaluated by the phase analysis method in myocardial perfusion imaging (MPI) or with cardiac ultrasound. The aim of this study was to investigate the reproducibility of phase analysis parameters in MPI and echocardiographic parameters in the evaluation of left ventricular mechanical dyssynchrony. In particular, the influence of BMI on reproducibility was studied. METHODS AND RESULTS: Twenty-one patients underwent an ECG-gated MPI scan. Acquisition was repeated after the rest image. The patients were also studied twice with transthoracic echocardiography. Of MPI phase analysis parameters bandwidth, histogram SD and entropy% were highly reproducible in the pooled population: Cronbach's α 0.927-0.967 and intraclass correlation (ICC) 0.868-0.967, (P<0.001 for all). However, the reproducibility of bandwidth and SD was poorer in patients with BMI≥29 kg/m group (α 0.203 and -0.055; ICC 0.106 and -0.027, NS for both) than in those with BMI<29 kg/m (α 0.984 and 0.980; ICC 0.968 and 0.961, P<0.001 for both). In contrast, BMI had no obvious influence on the reproducibility of global longitudinal strain in echocardiography. CONCLUSION: Parameters reflecting mechanical dyssynchrony were found to be well reproducible. However, this study indicates that phase analysis results may be less reproducible in patients with high BMI, whereas global longitudinal strain in echocardiography seems to be less critical for a patient's BMI.

Prediction of density and mechanical properties of human trabecular bone in vitro by using ultrasound transmission and backscattering measurements at 0.2-6.7 MHz frequency range.

The ultrasound (US) backscattering method has been introduced as an alternative for the through-transmission measurement of sound attenuation and speed in diagnosis of osteoporosis. Both attenuation and backscattering depend strongly on the US frequency. In this study, 20 human trabecular bone samples were measured in transmission and pulse-echo geometry in vitro. The aim of the study was to find the most sensitive frequency range for the quantitative ultrasound (QUS) analyses. Normalized broadband US attenuation (nBUA), speed of sound (SOS), broadband US backscatter (BUB) and integrated reflection coefficient (IRC) were determined for each sample. The samples were spatially scanned with five pairs of US transducers covering a frequency range of 0.2-6.7 MHz. Furthermore, mechanical properties and density of the same samples were determined. At all frequencies, SOS, BUB and IRC showed statistically significant linear correlations with the mechanical properties or density of human trabecular bone (0.51 < r < 0.82, 0.54 < r < 0.81 and 0.70 < r < 0.85, respectively). In contrast to SOS, IRC and BUB, nBUA showed statistically significant correlations with mechanical parameters or density at the centre frequency of 1 MHz only. Our results suggest that frequencies up to 5 MHz can be useful in QUS analyses for the prediction of bone mechanical properties and density. Since the use of higher frequencies provides better axial and spatial resolution, improved structural analyses may be possible. While extensive attenuation of high frequencies in trabecular bone limits the clinically feasible frequency range, selection of optimal frequency range for in vivo QUS application should be carefully considered.

A novel respiratory gating method for oncologic positron emission tomography based on bioimpedance approach.

OBJECTIVE: Respiratory motion causes loss of image quality and inaccuracy of quantification in oncologic positron emission tomography (PET) imaging. This study introduces a bioimpedance-based gating method for compensation of respiratory motion artefacts. METHODS: The bioimpedance-based respiratory gating method was studied parallel to a clinically used respiratory gating method [Real-time Position Management by Varian Medical Systems] in 4D PET/CT acquisition of 9 oncologic patients. The quantitative analysis consisted of the evaluation of tumour SUVpeak, SUVmax and volume. Additionally, target-to-background ratios as well as motion in cranial-caudal and anterior-posterior directions were measured. The evaluation was performed with amplitude- and time-based gating using averaged attenuation correction maps. RESULTS: Bioimpedance gating resulted in 17.7-18.9 % increase in mean SUVpeak and 20.0-21.4 % decrease in mean volume compared to non-gated images. The maximum motion measured from the bioimpedance-gated images was 19 mm in cranial-caudal direction and 9 mm in anterior-posterior direction. CONCLUSIONS: Bioimpedance-based respiratory gating compensates the adverse effects of motion in oncologic PET imaging.

Assessment of body composition by dual-energy X-ray absorptiometry, bioimpedance analysis and anthropometrics in children: the Physical Activity and Nutrition in Children study.

OBJECTIVE AND METHODS: We compared InBody720 segmental multifrequency bioimpedance analysis (SMF-BIA) with Lunar Prodigy Advance dual-energy X-ray absorptiometry (DXA) in assessment of body composition among 178 predominantly prepubertal children. Segmental agreement analysis of body compartments was carried out, and inter-relationships of anthropometric and other measures of body composition were defined. Moreover, the relations of different reference criteria for excess body fat were evaluated. RESULTS: The prevalence of excess body fat varies greatly according to the used criteria. Intraclass and Pearson's correlations between SMF-BIA and DXA were >0·92 in total body and >0·74 in regional measures. SMF-BIA underestimated percentage body fat (%BF) and fat mass (FM), and overestimated lean mass (LM) and percentage LM with significant offset trend bias. Higher adiposity increased offsets, and overall agreement was poorer in girls. On average, %BF offsets (girls/boys) and limits of agreement (LA) were 3·9/1·6% [(-)1·4-9·2%/(-)3·4-6·7%]. Interestingly percentage offsets of fat content (%BF: 18·9/10·1%, FM: 18·8/11·1%) showed no significant bias trends indicating that the corresponding absolute methodological offset depends on the amount of fat content. The smallest percentage offset was found with LM: 4·3/0·1%, referring offset (LA) of 0·88/0·03 kg (±2·05/±1·71 kg). Correspondingly, segmental LM had poorer agreement than total body LM. All anthropometrics except for the waist-to-hip ratio showed strong correlations (r = 0·76-0·95) with abdominal and total body fat. CONCLUSION: Segmental multifrequency bioimpedance analysis is precise enough for total-LM analysis and had also sufficient trueness for total body composition analysis to be used in epidemiological purposes. There is need to generate scientifically and clinically relevant criteria and reference values for excess body fat.

Ability of ultrasound backscattering to predict mechanical properties of bovine trabecular bone.

Ultrasound (US) backscatter measurements have been proposed for the quantitative evaluation of bone quality. In this study, we explored the ability of broadband US backscatter (BUB) and integrated reflection coefficient (IRC) to predict density and mechanical properties of trabecular bone, as compared to normalized broadband US attenuation (nBUA) and speed of sound (SOS). These acoustic parameters were measured in 41 in vitro samples of bovine trabecular bone and correlated with a number of mechanical parameters and with volumetric bone mineral density (BMDvol). BUB correlated statistically significantly with the volumetric bone mineral density (r = 0.61, p < 0.01), Young's modulus (r = 0.40, p < 0.01) and ultimate strength (r = 0.40, p < 0.01). IRC was even more strongly correlated with BMD(vol) (r = 0.92, p < 0.01) and most of the mechanical parameters (0.81 < r < 0.85). Strong correlations were also found between mechanical parameters and SOS (0.87 < r < 0.90). No significant correlation was found between attenuation (nBUA) and either BMD(vol) or mechanical parameters. Reproducibilities (standardized CV%) of BUB (3.5%) and IRC (1.5%) were comparable to those of nBUA (2.3%) and SOS (0.5%). To conclude, BUB and IRC are promising parameters for the evaluation of density and mechanical properties of trabecular bone. Advantageously, BUB and IRC can be determined with a single transducer, hypothetically enabling measurements at many clinically relevant fracture sites.