Stiffness and Strain Properties Derived From Digital Tomosynthesis-Based Digital Volume Correlation Predict Vertebral Strength Independently From Bone Mineral Density.

Vertebral fractures are the most common osteoporotic fractures, but their prediction using standard bone mineral density (BMD) measurements from dual energy X-ray absorptiometry (DXA) is limited in accuracy. Stiffness, displacement, and strain distribution properties derived from digital tomosynthesis-based digital volume correlation (DTS-DVC) have been suggested as clinically measurable metrics of vertebral bone quality. However, the extent to which these properties correlate to vertebral strength is unknown. To establish this relationship, two independent experiments, one examining isolated T11 and the other examining L3 vertebrae within the L2-L4 segments from cadaveric donors were utilized. Following DXA and DTS imaging, the specimens were uniaxially compressed to fracture. BMD, bone mineral content (BMC), and bone area were recorded for the anteroposterior and lateromedial views from DXA, stiffness, endplate to endplate displacement and distribution statistics of intravertebral strains were calculated from DTS-DVC and vertebral strength was measured from mechanical tests. Regression models were used to examine the relationships of strength with the other variables. Correlations of BMD with vertebral strength varied between experimental groups (R2adj = 0.19-0.78). DTS-DVC derived properties contributed to vertebral strength independently from BMD measures (increasing R2adj to 0.64-0.95). DTS-DVC derived stiffness was the best single predictor (R2adj = 0.66, p < 0.0001) and added the most to BMD in models of vertebral strength for pooled T11 and L3 specimens (R2adj = 0.95, p < 0.0001). These findings provide biomechanical relevance to DTS-DVC calculated properties of vertebral bone and encourage further efforts in the development of the DTS-DVC approach as a clinical tool.

Assessment of Intravertebral Mechanical Strains and Cancellous Bone Texture Under Load Using a Clinically Available Digital Tomosynthesis Modality.

Vertebral fractures are the most common osteoporotic fractures, but clinical means for assessment of vertebral bone integrity are limited in accuracy, as they typically use surrogate measures that are indirectly related to mechanics. The objective of this study was to examine the extent to which intravertebral strain distributions and changes in cancellous bone texture generated by a load of physiological magnitude can be characterized using a clinically available imaging modality. We hypothesized that digital tomosynthesis-based digital volume correlation (DTS-DVC) and image texture-based metrics of cancellous bone microstructure can detect development of mechanical strains under load. Isolated cadaveric T11 vertebrae and L2-L4 vertebral segments were DTS imaged in a nonloaded state and under physiological load levels. Axial strain, maximum principal strain, maximum compressive and tensile principal strains, and von Mises equivalent strain were calculated using the DVC technique. The change in textural parameters (line fraction deviation, anisotropy, and fractal parameters) under load was calculated within the cancellous centrum. The effect of load on measured strains and texture variables was tested using mixed model analysis of variance, and relationships of strain and texture variables with donor age, bone density parameters, and bone size were examined using regression models. Magnitudes and heterogeneity of intravertebral strain measures correlated with applied loading and were significantly different from background noise. Image texture parameters were found to change with applied loading, but these changes were not observed in the second experiment testing L2-L4 segments. DTS-DVC-derived strains correlated with age more strongly than did bone mineral density (BMD) for T11.

Challenges and Opportunities in the Clinical Development of Immune Checkpoint Inhibitors for Hepatocellular Carcinoma.

After a decade of stagnation in drug development, therapeutic reversal of immune-exhaustion with immune checkpoint inhibitors (ICPIs) has been shown to be effective in advanced hepatocellular carcinoma (HCC). The clinical development of novel ICPIs continues at a rapid pace, with more than 50 clinical trials of immunotherapeutic agents registered as of May 2018 for this indication. The development of ICPI is particularly challenging in patients with HCC, a population with unique features which impact on safety and efficacy of immune-modulating therapies. In this review, we discuss the biological foundations supporting the development of ICPIs across the advancing stages of HCC, focusing on the rational positioning of ICPIs across the various Barcelona-Clinic Liver Cancer (BCLC) stages of the disease. Translational studies should guide adequate prioritization of those therapeutic agents and combination strategies which are most likely to achieve patient benefit based on solid mechanistic and clinical justifications.

Digital Tomosynthesis and Fractal Analysis Predict Prevalent Vertebral Fractures in Patients With Multiple Myeloma: A Preliminary In Vivo Study.

OBJECTIVE. The objective of this study was to investigate the association of fractal-derived bone microstructural parameters with vertebral fracture status using in vivo digital tomosynthesis images of the spine. MATERIALS AND METHODS. Digital tomosynthesis images of the thoracic and lumbar spine from T1 to L5 were acquired from 36 patients with newly diagnosed multiple myeloma or monoclonal gammopathy of uncertain significance (age range, 39-85 years old). Scans were performed with patients in the supine position with reconstructed planes formed in the coronal direction. Bone mineral density (BMD) was recorded for 10 patients who had recently undergone dual x-ray absorptiometry. Vertebral fracture and lytic lesion status was determined by a radiologist from digital radiographs. Radiologist interpretation was reviewed to identify levels with a minimum number of fractures or lesions. For fractal analysis, the largest possible cuboid volume of interest within the cancellous bone was cropped from T7 and T11 images. Mean and SD of fractal variables between slices of fractal dimension (FD, a measure of self-similarity in the texture), mean lacunarity (λ, a measure of heterogeneity) and the slope of lacunarity versus box size relationship (Sλ, a measure of sensitivity of heterogeneity to size scale) were calculated using a box-counting method. A generalized estimating equation (GEE) platform was used to examine fractal variables as predictors of fracture status. RESULTS. Fracture status was not significantly associated with sex, race, age, stage of myeloma, presence of lesion in the spine, or BMD. In light of these results, no correction was made for these variables in further analyses of fractal variables. No interaction was found between vertebral level and any of the fractal variables (p = 0.12-0.77). Therefore, vertebral level was not considered further as an independent variable. Logistic regression analysis within GEE indicated that probability of fracture decreased with increasing mean FD (p = 0.02). In contrast, probability of fracture increased with increasing mean λ (p = 0.03). Although not to a statistically significant degree, probability of fracture increased with increasing mean Sλ (p = 0.08), SD of FD (p = 0.07), SD of λ (p = 0.07), and SD of Sλ (p = 0.06). CONCLUSION. We found FD and lacunarity calculated within the cancellous centrum of T7 and T11 vertebrae to be significantly associated with the presence of a vertebral fracture in this cohort. The decreased probability of fracture with increasing fractal dimension and increased probability of fracture with increasing lacunarity are consistent with the idea that cancellous bone with a better organized trabecular architecture is mechanically more competent. To our knowledge, this is the first in vivo evidence that fractal analysis of vertebral bone from tomosynthesis images may be useful in assessing vertebral fracture risk in patients with multiple myeloma.

The emerging role of anti-CD25 directed therapies as both immune modulators and targeted agents in cancer.

CD25 (also termed IL2RA) forms one component of the high-affinity heterotrimeric interleukin 2 (IL2) receptor on activated T cells. Its affinity for IL2 and cellular function are tightly regulated and vary in different cell types. The high frequency of CD25 on the surface of many different haematological tumour cells is now well established and, apart from its prognostic significance, CD25 may be present on leukaemic stem cells and enable oncogenic signalling pathways in leukaemic cells. Additionally, high CD25 expression in activated circulating immune cells and Tregs is a factor that has already been exploited by IL2 immunotherapies for treatment of tumours and autoimmune disease. The relative clinical safety and efficacy of administering anti-CD25 radioimmunoconjugates and immunotoxins in various haematological tumour indications has been established and clinical trials of a novel CD25-directed antibody drug conjugate are underway.

Body Size-Specific Organ and Effective Doses of Chest CT Screening Examinations of the National Lung Screening Trial.

OBJECTIVE: We calculated body size-specific organ and effective doses for 23,734 participants in the National Lung Screening Trial (NLST) using a CT dose calculator. MATERIALS AND METHODS: We collected participant-specific technical parameters of 23,734 participants who underwent CT in the clinical trial. For each participant, we calculated two sets of organ doses using two methods. First, we computed body size-specific organ and effective doses using the National Cancer Institute CT (NCICT) dosimetry program, which is based on dose coefficients derived from a library of body size-dependent adult male and female computational phantoms. We then recalculated organ and effective doses using dose coefficients from reference size phantoms for all examinations to investigate potential errors caused by the lack of body size consideration in the dose calculations. RESULTS: The underweight participants (body mass index [BMI; weight in kilograms divided by the square of height in meters] < 18.5) received 1.3-fold greater lung dose (median, 4.93 mGy) than the obese participants (BMI > 30) (3.90 mGy). Thyroid doses were approximately 1.3- to 1.6-fold greater than the lung doses (6.3-6.5 mGy). The reference phantom-based dose calculation underestimates the body size-specific lung dose by up to 50% for the underweight participants and overestimates that value by up to 200% for the overweight participants. The median effective dose ranges from 2.01 mSv in obese participants to 2.80 mSv in underweight participants. CONCLUSION: Body size-specific organ and effective doses were computed for 23,734 NLST participants who underwent low-dose CT screening. The use of reference size phantoms can lead to significant errors in organ dose estimates when body size is not considered in the dose assessment.

Consistency and standardization of color in medical imaging: a consensus report.

This article summarizes the consensus reached at the Summit on Color in Medical Imaging held at the Food and Drug Administration (FDA) on May 8-9, 2013, co-sponsored by the FDA and ICC (International Color Consortium). The purpose of the meeting was to gather information on how color is currently handled by medical imaging systems to identify areas where there is a need for improvement, to define objective requirements, and to facilitate consensus development of best practices. Participants were asked to identify areas of concern and unmet needs. This summary documents the topics that were discussed at the meeting and recommendations that were made by the participants. Key areas identified where improvements in color would provide immediate tangible benefits were those of digital microscopy, telemedicine, medical photography (particularly ophthalmic and dental photography), and display calibration. Work in these and other related areas has been started within several professional groups, including the creation of the ICC Medical Imaging Working Group.

Developing an objective marker to optimize patient selection and predict survival benefit in early-phase cancer trials.

BACKGROUND: Several prognostic indices have been devised to optimize patient selection for phase 1 oncology trials with no consensus as to the optimal score and none qualifying as a marker of treatment response. METHODS: Multivariate predictors of overall survival (OS) were tested on 118 referred patients to develop the Hammersmith Score (HS). The score's ability to predict OS, progression-free survival (PFS), and 90-day mortality (90DM) was compared with other prognostic indices. Changes in HS were recalculated during treatment. RESULTS: Albumin<35 g/L, lactate dehydrogenase>450 U/L, and sodium<135 mmol/L emerged as independent prognostic factors. These were used with equal weighting to devise the HS, a compound prognostic index ranging from 0 to 3. High (HS=2-3) score predicted worse OS (hazard ratio [HR]=6.5, P<.001), PFS (HR=2.8, P=.01), and 90DM (OR=9.0, P<.001). HS was a more accurate multivariate predictor of OS (HR=6.4, P<.001, C-index=0.72), PFS (HR=2.7, P=.03), and 90DM (area under the ROC curve 0.703) compared with other scores. Worsening of the HS during treatment predicted for shorter OS (P<.001). HS retained prognostic and predictive ability following external validation. CONCLUSIONS: HS is a simple, validated index to optimize patient selection and predict survival benefit from phase 1 oncology treatments. Prospective validation is ongoing.

miRNA circuit modules for precise, tunable control of gene expression.

The ability to express transgenes at specified levels is critical for understanding cellular behaviors, and for applications in gene and cell therapy. Transfection, viral vectors, and other gene delivery methods produce varying protein expression levels, with limited quantitative control, while targeted knock-in and stable selection are inefficient and slow. Active compensation mechanisms can improve precision, but the need for additional proteins or lack of tunability have prevented their widespread use. Here, we introduce a toolkit of compact, synthetic miRNA-based circuit modules that provide precise, tunable control of transgenes across diverse cell types. These circuits, termed DIMMERs (Dosage-Invariant miRNA-Mediated Expression Regulators) use multivalent miRNA regulatory interactions within an incoherent feed-forward loop architecture to achieve nearly uniform protein expression over more than two orders of magnitude variation in underlying gene dosages or transcription rates. They also allow coarse and fine control of expression, and are portable, functioning across diverse cell types. In addition, a heuristic miRNA design algorithm enables the creation of orthogonal circuit variants that independently control multiple genes in the same cell. These circuits allowed dramatically improved CRISPR imaging, and super-resolution imaging of EGFR receptors with transient transfections. The toolbox provided here should allow precise, tunable, dosage-invariant expression for research, gene therapy, and other biotechnology applications.

Synthetic dosage-compensating miRNA circuits allow precision gene therapy for Rett syndrome.

A longstanding challenge in gene therapy is expressing a dosage-sensitive gene within a tight therapeutic window. For example, loss of MECP2 function causes Rett syndrome, while its duplication causes MECP2 duplication syndrome. Viral gene delivery methods generate variable numbers of gene copies in individual cells, creating a need for gene dosage-invariant expression systems. Here, we introduce a compact miRNA-based, incoherent feed-forward loop circuit that achieves precise control of Mecp2 expression in cells and brains, and improves outcomes in an AAV-based mouse model of Rett syndrome gene therapy. Single molecule analysis of endogenous and ectopic Mecp2 mRNA revealed precise, sustained expression across a broad range of gene dosages. Delivered systemically in a brain-targeting AAV capsid, the circuit strongly suppressed Rett behavioral symptoms for over 24 weeks, outperforming an unregulated gene therapy. These results demonstrate that synthetic miRNA-based regulatory circuits can enable precise in vivo expression to improve the safety and efficacy of gene therapy.

Effective dose assessment for participants in the National Lung Screening Trial undergoing posteroanterior chest radiographic examinations.

OBJECTIVE: The National Lung Screening Trial (NLST) is a multicenter randomized controlled trial comparing low-dose helical CT with chest radiography in the screening of older current and former heavy smokers for early detection of lung cancer. Recruitment was launched in September 2002 and ended in April 2004, when 53,454 participants had been randomized at 33 screening sites. The objective of this study was to determine the effective radiation dose associated with individual chest radiographic screening examinations. SUBJECTS AND METHODS: A total of 73,733 chest radiographic examinations were performed with 92 chest imaging systems. The entrance skin air kerma (ESAK) of participants' chest radiographic examinations was estimated and used in this analysis. The effective dose per ESAK for each examination was determined with a Monte Carlo-based program. The examination effective dose was calculated as the product of the examination ESAK and the Monte Carlo estimate of the ratio of effective dose per ESAK. RESULTS: This study showed that the mean effective dose assessed from 66,157 postero-anterior chest examinations was 0.052 mSv. Additional findings were a median effective dose of 0.038 mSv, a 95th percentile value of 0.136 mSv, and a fifth percentile value of 0.013 mSv. CONCLUSION: The effective dose for participant NLST chest radiographic examinations was determined and is of specific interest in relation to that associated with the previously published NLST low-dose CT examinations conducted during the trial.

Ovarian cancer recurrence: is the definition of platinum resistance modified by PARPi and other intervening treatments? The evolving landscape in the management of platinum-resistant ovarian cancer.

Definitions of platinum resistance have been questioned and changed over the last five years, even though no predictive biomarker of resistance exists. These have sculpted how we approach platinum retreatment and, consequently, how we devise new treatment strategies for those patients with tumour progression on platinum therapy. Platinum-non-eligible ovarian cancer is treated with single-agent non-platinum drugs. When bevacizumab can be added to chemotherapy, progression-free survival improves significantly. For patients with a BRCA mutation, PARP inhibitor monotherapy is an option compared to chemotherapy. There is currently no clearly identified role for immune-checkpoint inhibition in this patient population. This review describes some of the challenges in treating patients with platinum resistance and suggests refinements in the selection of patients most likely to benefit from targeting a DNA damage response, angiogenesis or immune modulation. It also describes novel agents of interest and possible mechanisms of the synergy of therapeutic combinations.

The relationship of whole human vertebral body creep to bone density and texture via clinically available imaging modalities.

Creep deformation of human vertebrae accumulates under physiological levels of load and is understood to contribute to the progression toward clinically observable vertebral fracture. However, little information is available in terms of clinically measurable predictors of creep behavior in human vertebrae. In this study, creep tests were performed on 22 human cadaveric T12 vertebrae (13 male, 9 female; age 41-90). Areal and volumetric bone density parameters were measured from the same specimens using dual x-ray absorptiometry and high resolution computed tomography. Image textural analyses (which probe the organization of image intensities within the cancellous bone in low resolution clinical imaging) were performed using digital tomosynthesis (DTS) images. Multiple regression models were constructed to examine the relationship between creep properties and bone density and DTS image textural parameters. For the standard clinical imaging configuration, models including DTS derived image textural parameters alone were generally more explanatory (adjusted R2: 0.14-0.68) than those with bone density parameters forced in the models (adjusted R2: 0.17-0.61). Metrics of textural heterogeneity and anisotropy presented as the most explanatory imaging markers for creep deformation and recovery from creep. These metrics of image texture may help provide, independent from bone mass, important clinically measurable indicators of the time dependent deformation of human vertebrae.

Measuring the thickness of vertebral endplate and shell using digital tomosynthesis.

The vertebral endplate and cortical shell play an important structural role and contribute to the overall strength of the vertebral body, are at highest risk of initial failure, and are involved in degenerative disease of the spine. The ability to accurately measure the thickness of these structures is therefore important, even if difficult due to relatively low resolution clinical imaging. We posit that digital tomosynthesis (DTS) may be a suitable imaging modality for measurement of endplate and cortical shell thickness owing to the ability to reconstruct multiplanar images with good spatial resolution at low radiation dose. In this study, for 25 cadaveric L1 vertebrae, average and standard deviation of endplate and cortical shell thickness were measured using images from DTS and microcomputed tomography (µCT). For endplate thickness measurements, significant correlations between DTS and µCT were found for all variables when comparing thicknesses measured in both the overall endplate volume (R2 = 0.25-0.54) and when measurements were limited to a central range of coronal or sagittal slices (R2 = 0.24-0.62). When compared to reference values from the overall shell volume, DTS thickness measurements were generally nonsignificant. However, when measurement of cortical shell thickness was limited to a range of central slices, DTS outcomes were significantly correlated with reference values for both sagittal and coronal central regions (R2 = 0.21-0.49). DTS may therefore offer a means for measurement of endplate thickness and, within a limited sagittal or coronal measurement volume, for measurement of cortical shell thickness.

Molecular characterization and identification of surrogate substrates for diacylglycerol lipase α.

Diacylglycerol lipase α is the key enzyme in the formation of the most prevalent endocannabinoid, 2-arachidonoylglycerol in the brain. In this study we identified the catalytic triad of diacylglycerol lipase α, consisting of serine 472, aspartate 524 and histidine 650. A truncated version of diacylglycerol lipase α, spanning residues 1-687 retains complete catalytic activity suggesting that the C-terminal domain is not required for catalysis. We also report the discovery and the characterization of fluorogenic and chromogenic substrates for diacylglycerol lipase α. Assays performed with these substrates demonstrate equipotent inhibition of diacylglycerol lipase α by tetrahydrolipastatin and RHC-20867 as compared to reactions performed with the native diacylglycerol substrate. Thus, confirming the utility of assays using these substrates for identification and kinetic characterization of inhibitors from pharmaceutical collections.

Estimated radiation dose associated with low-dose chest CT of average-size participants in the National Lung Screening Trial.

OBJECTIVE: The objective of our study was to determine the distribution of effective dose associated with a single low-dose CT chest examination of average-size participants in the National Lung Screening Trial. Organ doses were also investigated. MATERIALS AND METHODS: Thirty-three sites nationwide provided volume CT dose index (CTDI(vol)) data annually for the 97 MDCT scanners used to image 26,724 participants during the trial. The dose data were representative of the imaging protocols used by the sites for average-size participants. Effective doses were estimated first using the product of the dose-length product (CTDI(vol) × 35-cm scan length) and a published conversion factor, "k." The commercial software product CT-Expo was then used to estimate organ doses to males and females from the average CTDI(vol). Applying tissue-weighting factors from both publication 60 and the more recent publication 103 of the International Commission on Radiological Protection (ICRP) allowed comparisons of effective doses to males and to females. RESULTS: The product of DLP and the k factor resulted in a mean effective dose of 1.4 mSv (SD = 0.5 mSv) for a low-dose chest examination across all scanners. The CT-Expo results based on ICRP 60 tissue-weighting factors yielded effective doses of 1.6 and 2.1 mSv for males and females, respectively, whereas CT-Expo results based on ICRP 103 tissue-weighting factors resulted in effective doses of 1.6 and 2.4 mSv, respectively. CONCLUSION: Acceptable chest CT screening can be accomplished at an overall average effective dose of approximately 2 mSv as compared with an average effective dose of 7 mSv for a typical standard-dose chest CT examination.

Technical innovation: digital tomosynthesis of the hip following intra-articular administration of contrast.

OBJECTIVE: To demonstrate the clinical use of digital tomosynthesis in the depiction of labral and chondral pathology in the setting of post-operative CAM-type impingement of the hip following intra-articular administration of dilute iodinated contrast. MATERIALS AND METHODS: We present images from a 46 year-old African American female with suspected CAM-type femoroacetabular impingement (FAI) following percutaneous pinning of the right hip for slipped capital femoral epiphysis (SCFE). RESULTS: A partial tear of the labrum and clinically significant acetabular chondral abnormalities were demonstrated with the use of digital tomosynthesis with superb anatomic detail. CONCLUSION: Digital tomosynthesis can be of great clinical utility and can depict pathology in superb anatomic detail, particularly in situations in which MRI is not available as well as under circumstances in which artifact due to orthopedic hardware is of concern as shown in this case.

Bone health assessment via digital wrist tomosynthesis in the mammography setting.

Bone fractures attributable to osteoporosis are a significant problem. Though preventative treatment options are available for individuals who are at risk of a fracture, a substantial number of these individuals are not identified due to lack of adherence to bone screening recommendations. The issue is further complicated as standard diagnosis of osteoporosis is based on bone mineral density (BMD) derived from dual energy x-ray absorptiometry (DXA), which, while helpful in identifying many at risk, is limited in fully predicting risk of fracture. It is reasonable to expect that bone screening would become more prevalent and efficacious if offered in coordination with digital breast tomosynthesis (DBT) exams, provided that osteoporosis can be assessed using a DBT modality. Therefore, the objective of the current study was to explore the feasibility of using digital tomosynthesis imaging in a mammography setting. To this end, we measured density, cortical thickness and microstructural properties of the wrist bone, correlated these to reference measurements from microcomputed tomography and DXA, demonstrated the application in vivo in a small group of participants, and determined the repeatability of the measurements. We found that measurements from digital wrist tomosynthesis (DWT) imaging with a DBT scanner were highly repeatable ex vivo (error = 0.05%-9.62%) and in vivo (error = 0.06%-10.2%). In ex vivo trials, DWT derived BMDs were strongly correlated with reference measurements (R = 0.841-0.980), as were cortical thickness measured at lateral and medial cortices (R = 0.991 and R = 0.959, respectively) and the majority of microstructural measures (R = 0.736-0.991). The measurements were quick and tolerated by human patients with no discomfort, and appeared to be different between young and old participants in a preliminary comparison. In conclusion, DWT is feasible in a mammography setting, and informative on bone mass, cortical thickness, and microstructural qualities that are known to deteriorate in osteoporosis. To our knowledge, this study represents the first application of DBT for imaging bone. Future clinical studies are needed to further establish the efficacy for diagnosing osteoporosis and predicting risk of fragility fracture using DWT.

An In-Depth Review of Niraparib in Ovarian Cancer: Mechanism of Action, Clinical Efficacy and Future Directions.

Niraparib is an oral, potent, highly selective poly-ADP ribose polymerase 1 (PARP1) and PARP2 inhibitor. In most developed countries, it is approved as a maintenance treatment for epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients with complete or partial response to platinum-based therapy. These approvals are based on results of randomised, double-blind, placebo-controlled trials, particularly the NOVA trial and more recently the PRIMA trial. In this comprehensive review, we delve into the scientific basis of PARP inhibition, discussing both preclinical and clinical data which have led to the current approval status of niraparib. We also discuss ongoing trials and biological rationale of combination treatments involving niraparib, with particular focus on antiangiogenic drugs, immune checkpoint inhibitors and cyclic GMP-AMP synthase stimulator of interferon genes (cGAS/STING) pathway. In addition, we reflect on potential strategies and challenges of utilising current biomarkers for treatment selection of patients to ensure maximal benefit.

Normalized CT dose index of the CT scanners used in the National Lung Screening Trial.

OBJECTIVE: The National Lung Screening Trial includes 33 participating institutions that performed 75,133 lung cancer screening CT examinations for 26,724 subjects during 2002-2007. For trial quality assurance reasons, CT radiation dose measurement data were collected from all MDCT scanners used in the trial. MATERIALS AND METHODS: A total of 247 measurements on 96 MDCT scanners were collected using a standard CT dose index (CTDI) measurement protocol. The scan parameters used in the measurements (tube voltage, milliampere-seconds [mAs], and detector-channel configuration) were set according to trial protocol for average size subjects. The normalized weighted CT dose index (CTDI(w)) (computed as CTDI(w)/mAs) obtained from each trial-participating scanner was tabulated. RESULTS: We found a statistically significant difference in normalized CT dose index among CT scanner manufacturers, likely as a result of design differences, such as filtration, bow-tie design, and geometry. Our findings also indicated a statistically significant difference in normalized CT dose index among CT scanner models from the same manufacturer (e.g., GE Healthcare, Siemens Healthcare, and Philips Healthcare). We also found a statistically significant difference in normalized CT dose index among all models and all manufacturers; furthermore, we found a statistically significant difference in normalized CT dose index among CT scanners from all manufacturers when we compared scanners with four or eight data channels to those with 16, 32, or 64 channels, suggesting that more complex scanners have improved dose efficiency. CONCLUSION: Average normalized CT dose index values varied by a factor of almost two for all scanners from all manufacturers. This study was focused on machine-specific normalized CT dose index; patient dose and image quality were not addressed.