First-in-class MKK4 inhibitors enhance liver regeneration and prevent liver failure.

Diminished hepatocyte regeneration is a key feature of acute and chronic liver diseases and after extended liver resections, resulting in the inability to maintain or restore a sufficient functional liver mass. Therapies to restore hepatocyte regeneration are lacking, making liver transplantation the only curative option for end-stage liver disease. Here, we report on the structure-based development and characterization (nuclear magnetic resonance [NMR] spectroscopy) of first-in-class small molecule inhibitors of the dual-specificity kinase MKK4 (MKK4i). MKK4i increased liver regeneration upon hepatectomy in murine and porcine models, allowed for survival of pigs in a lethal 85% hepatectomy model, and showed antisteatotic and antifibrotic effects in liver disease mouse models. A first-in-human phase I trial (European Union Drug Regulating Authorities Clinical Trials [EudraCT] 2021-000193-28) with the clinical candidate HRX215 was conducted and revealed excellent safety and pharmacokinetics. Clinical trials to probe HRX215 for prevention/treatment of liver failure after extensive oncological liver resections or after transplantation of small grafts are warranted.

Diagnostic Performance in Low- and High-Contrast Tasks of an Image-Based Denoising Algorithm Applied to Radiation Dose-Reduced Multiphase Abdominal CT Examinations.

BACKGROUND. Anatomic redundancy between phases can be used to achieve denoising of multiphase CT examinations. A limitation of iterative reconstruction (IR) techniques is that they generally require use of CT projection data. A frequency-split multi-band-filtration algorithm applies denoising to the multiphase CT images themselves. This method does not require knowledge of the acquisition process or integration into the reconstruction system of the scanner, and it can be implemented as a supplement to commercially available IR algorithms. OBJECTIVE. The purpose of the present study is to compare radiologists' performance for low-contrast and high-contrast diagnostic tasks (i.e., tasks for which differences in CT attenuation between the imaging target and its anatomic background are subtle or large, respectively) evaluated on multiphase abdominal CT between routine-dose images and radiation dose-reduced images processed by a frequency-split multiband-filtration denoising algorithm. METHODS. This retrospective single-center study included 47 patients who underwent multiphase contrast-enhanced CT for known or suspected liver metastases (a low-contrast task) and 45 patients who underwent multiphase contrast-enhanced CT for pancreatic cancer staging (a high-contrast task). Radiation dose-reduced images corresponding to dose reduction of 50% or more were created using a validated noise insertion technique and then underwent denoising using the frequency-split multi-band-filtration algorithm. Images were independently evaluated in multiple sessions by different groups of abdominal radiologists for each task (three readers in the low-contrast arm and four readers in the high-contrast arm). The noninferiority of denoised radiation dose-reduced images to routine-dose images was assessed using the jackknife alternative free-response ROC (JAFROC) figure-of-merit (FOM; limit of noninferiority, -0.10) for liver metastases detection and using the Cohen kappa statistic and reader confidence scores (100-point scale) for pancreatic cancer vascular invasion. RESULTS. For liver metastases detection, the JAFROC FOM for denoised radiation dose-reduced images was 0.644 (95% CI, 0.510-0.778), and that for routine-dose images was 0.668 (95% CI, 0.543-0.792; estimated difference, -0.024 [95% CI, -0.084 to 0.037]). Intraobserver agreement for pancreatic cancer vascular invasion was substantial to near perfect when the two image sets were compared (κ = 0.53-1.00); the 95% CIs of all differences in confidence scores between image sets contained zero. CONCLUSION. Multiphase contrast-enhanced abdominal CT images with a radiation dose reduction of 50% or greater that undergo denoising by a frequency-split multiband-filtration algorithm yield performance similar to that of routine-dose images for detection of liver metastases and vascular staging of pancreatic cancer. CLINICAL IMPACT. The image-based denoising algorithm facilitates radiation dose reduction of multiphase examinations for both low- and high-contrast diagnostic tasks without requiring manufacturer-specific hardware or software.

Technical note: Evaluation of artificial 120-kilovolt computed tomography images for radiation therapy applications.

PURPOSE: The purpose of this work is to evaluate the scaled computed tomography (CT) number accuracy of an artificial 120 kV reconstruction technique based on phantom experiments in the context of radiation therapy planning. METHODS: An abdomen-shaped electron density phantom was scanned on a clinical CT scanner capable of artificial 120 kV reconstruction using different tube potentials from 70 to 150 kV. A series of tissue-equivalent phantom inserts (lung, adipose, breast, solid water, liver, inner bone, 30%/50% CaCO3 , cortical bone) were placed inside the phantom. Images were reconstructed using a conventional quantitative reconstruction kernel as well as the artificial 120 kV reconstruction kernel. Scaled CT numbers of inserts were measured from images acquired at different kVs and compared with those acquired at 120 kV, which were deemed as the ground truth. The relative error was quantified as the percentage deviation of scaled CT numbers acquired at different tube potentials from their ground truth values acquired at 120 kV. RESULTS: Scaled CT numbers measured from images reconstructed using the conventional reconstruction demonstrated a strong kV-dependence. The relative error in scaled CT numbers ranged from 0.6% (liver insert) to 31.1% (cortical bone insert). The artificial 120 kV reconstruction reduced the kV dependence, especially for bone tissues. The relative error in scaled CT number was reduced to 0.4% (liver insert) and 2.6% (30% CaCO3 insert) using this technique. When tube potential selection was limited to the range of 90 to 150 kV, the relative error was further restrained to <1.2% for all tissue types. CONCLUSION: Phantom results demonstrated that using the artificial 120 kV technique, it was feasible to acquire raw projection data at the desired tube potential and then reconstruct images with scaled CT numbers comparable to those obtained directly at 120 kV. In radiotherapy applications, this technique may allow optimization of tube potential without complicating clinical workflow by eliminating the necessity of maintaining multiple sets of CT calibration curves.

Characterization of thrombus composition with multimodality CT-based imaging: an in-vitro study.

BACKGROUND: CT is the most commonly used imaging modality for acute ischemic stroke evaluation. There is growing interest to use pre-operative imaging to characterize clot composition in stroke. We performed an in-vitro study examining the ability of various CT techniques in differentiation between different clot types. METHODS: Five clot types with varying fibrin and red blood cells (RBCs) densities (5% RBC and 95% fibrin; 25% RBC and 75% fibrin; 50% RBC and 50% fibrin; 75% RBC and 25% fibrin; 95% RBC and 5% fibrin) were prepared and scanned using various CT scanning protocols (single-energy, dual-energy, photon-counting detector CT, mixed images, and virtual monoenergetic images). Martius Scarlett Blue trichrome staining was performed to confirm the composition of each clot. Mean CT values of each type of clot under different scanning protocol were calculated and compared. RESULTS: Mean CT values of the CT numbers in the five clot specimens for 5%, 25%, and 50% RBC clot were similar across modalities, and increased significantly for 75% and 95% RBC clots (P<0.0001). Mean CT values are highest in the Mono +50 keV images in each type of clot, and they were also significantly higher than all other imaging protocols (P<0.001). Dual-energy CT with Mono +50 keV images showed the greatest difference between attenuation in each type of clot. CONCLUSION: Mono +50 keV dual-energy CT scan may be helpful for differentiating between RBC-rich and fibrin-rich thrombi seen in large-vessel occlusion patients.

Preconditioning with Foam-mediated External Suction on Flap Microvasculature and Perfusion in a Rodent Model.

Foam-mediated external suction (FMES) has previously shown to improve tissue microcirculation. We hypothesized that preconditioning fasciocutaneous perforator flaps with FMES would augment perfusion and demonstrate greater capillary recruitment. METHODS: Gluteal perforator flaps were designed on sixteen 400 g rats. Continuous FMES at -125 mm Hg was applied on one side (intervention) to precondition tissue for 5 days, with the contralateral side as a paired control. In group A, we assessed changes following pretreatment, after surgery, and 7 days postprocedure, and in group B, we evaluated changes during preconditioning alone. In group A (N = 8), control and intervention flaps were assessed using laser-assisted indocyanine green fluorescence angiography. In group B, flap regions were assessed using 4-dimensional computed tomographic angiography. All flaps were analyzed for microvessel density using micro-computed tomography and histological assessment using hematoxylin and eosin and CD3 immunohistochemistry. RESULTS: Thirty-two flaps were included in this study (N = 16 intervention and matched controls). Four-dimensional computed tomographic angiography demonstrated 17% greater tissue perfusion in preconditioned flaps (mean, 78.7 HU; SD, 8.8) versus controls (mean, 67.3 HU; SD, 15.7; P < 0.01). Laser-assisted indocyanine green fluorescence angiography showed a 30% higher mean absolute intensity in preconditioned flaps versus controls (P < 0.01). Postsurgery mean absolute intensity in preconditioned flaps remained 21% higher than in controls (P = 0.03). Preconditioned flaps demonstrated a 2-fold increase in mean vessel volume of 9.1 mm3 (SD, 7) versus 4.5 mm3 (SD, 3) in controls (P = 0.04); there was a 33% higher mean area fraction of CD31 in preconditioned flaps, 3.9% (SD, 3) versus 2.9% (SD, 3) in controls (P = 0.03). CONCLUSION: FMES preconditioning has the potential to augment vascularity of tissue for flap harvest; however, further experimental studies are required to optimize strategies and evaluate long-term effects for clinical applications.

Clinical utility of virtual noncalcium dual-energy CT in imaging of the pelvis and hip.

Dual-energy virtual noncalcium images are increasingly used to identify marrow edema which accompanies bony pelvic injuries and marrow pathology obscured by cancellous bone. We present a clinical perspective of our experience using virtual noncalcium images in the work up of pelvic osseous pathology.

Dual-Energy CT Monitoring of Cryoablation Zone Growth in the Spinal Column and Bony Pelvis: A Laboratory Study.

PURPOSE: To evaluate the use of dual-energy computed tomography (CT) virtual noncalcium imaging (VNCa) to visualize ice ball growth during skeletal cryoablation procedures in the spine and bony pelvis. MATERIALS AND METHODS: Cryoablation was performed in the spine and bony pelvis of swine and human cadavers at 5 and 6 locations, respectively. CT scans were acquired every 2 minutes using a dual-source dual-energy scanner. Artifacts were suppressed using iterative metal artifact reduction, and ablation zones in the bones and surrounding tissue were visualized using multiplanar VNCa and mixed kV imaging. For each probe location and time point, ice detectability was determined and the volume of the ice was measured. RESULTS: At each location, ice was visualized within the bone before reaching critical neural and intraabdominal structures. Within bone, the ice ball could not be visualized on mixed kV images, but was seen using VNCa images before reaching the adjacent soft tissue in 7/11 (64%) scenarios. Volume of the smallest ice ball seen in VNCa images was 18% of the final volume after cryoablation compared with 42% for mixed kV (P = .014). CONCLUSIONS: This application of dual-energy CT and VNCa imaging to cryoablation monitoring permits earlier ice visualization within the vertebral column and pelvic bones in near real time. Because these scanners and imaging techniques increase in availability in interventional suites, cryoablation of tumors along the spine and pelvic bone potentially could be performed with greater confidence.

Reappraisal of Perforasomes of the Superficial Femoral, Descending Genicular, and Saphenous Arteries and Clinical Applications to Locoregional Reconstruction.

BACKGROUND: The superficial femoral artery and medial thigh region has been an underused donor site for perforator flaps. This study evaluated perforasomes of the superficial femoral artery and its principal branches to review the clinical applications for locoregional reconstruction. METHODS: Twenty-six fresh cadaveric lower extremities were dissected. Perforator size and anatomical course from the superficial femoral artery, descending genicular artery, and saphenous artery branch were documented. Perforators were selectively injected with iodinated contrast to assess vascular territories using computed tomography. A retrospective chart review was conducted on consecutive patients (2014 to 2015). RESULTS: One hundred thirty perforators were mapped in the medial thigh region. Eleven extended medial thigh perforator flaps and 15 hemicircumferential flaps were harvested. The mean distance from the joint line was 16.7 ± 7.3 cm. Perforators arose from the superficial femoral artery (62 percent), saphenous artery branch (23 percent), and descending genicular artery (15 percent). Superficial femoral artery perforators were located around the mid and proximal thigh region (p < 0.001). The median perforasome surface area was 244 cm, representing 36 percent in hemithigh flaps with preferential filling in the anteromedial region. Proximal perforasomes were the smallest. Perforasome areas based on vessel origin were comparable; however, saphenous artery perforators had a broader perforasome compared with descending genicular (p = 0.01) and superficial femoral artery perforators (p = 0.04). Six clinical case examples were presented for knee, thigh, and lower leg reconstruction. CONCLUSIONS: The superficial femoral artery or its branches can provide nontraditional reconstructive perforator flap options in regional reconstruction. They can be simple to harvest using a free-style approach, do not require preoperative imaging, offer a one-stage reconstructive method with low morbidity, and obviate the need for microsurgery or muscle flaps.

Low kV versus dual-energy virtual monoenergetic CT imaging for proven liver lesions: what are the advantages and trade-offs in conspicuity and image quality? A pilot study.

PURPOSE: Single-energy low tube potential (SE-LTP) and dual-energy virtual monoenergetic (DE-VM) CT images both increase the conspicuity of hepatic lesions by increasing iodine signal. Our purpose was to compare the conspicuity of proven liver lesions, artifacts, and radiologist preferences in dose-matched SE-LTP and DE-VM images. METHODS: Thirty-one patients with 72 proven liver lesions (21 benign, 51 malignant) underwent full-dose contrast-enhanced dual-energy CT (DECT). Half-dose images were obtained using single tube reconstruction of the dual-source SE-LTP projection data (80 or 100 kV), and by inserting noise into dual-energy projection data, with DE-VM images reconstructed from 40 to 70 keV. Three blinded gastrointestinal radiologists evaluated half-dose SE-LTP and DE-VM images, ranking and grading liver lesion conspicuity and diagnostic confidence (4-point scale) on a per-lesion basis. Image quality (noise, artifacts, sharpness) was evaluated, and overall image preference was ranked on per-patient basis. Lesion-to-liver contrast-to-noise ratio (CNR) was compared between techniques. RESULTS: Mean lesion size was 1.5 ± 1.2 cm. Across the readers, the mean conspicuity ratings for 40, 45, and 50 keV half-dose DE-VM images were superior compared to other half-dose image sets (p < 0.0001). Per-lesion diagnostic confidence was similar between half-dose SE-LTP compared to half-dose DE-VM images (p ≥ 0.05; 1.19 vs. 1.24-1.32). However, SE-LTP images had less noise and artifacts and were sharper compared to DE-VM images less than 70 keV (p < 0.05). On a per-patient basis, radiologists preferred SE-LTP images the most and preferred 40-50 keV the least (p < 0.0001). Lesion CNR was also higher in SE-LTP images than DE-VM images (p < 0.01). CONCLUSION: For the same applied dose level, liver lesions were more conspicuous using DE-VM compared to SE-LTP; however, SE-LTP images were preferred more than any single DE-VM energy level, likely due to lower noise and artifacts.

Low-dose CT for the detection and classification of metastatic liver lesions: Results of the 2016 Low Dose CT Grand Challenge.

PURPOSE: Using common datasets, to estimate and compare the diagnostic performance of image-based denoising techniques or iterative reconstruction algorithms for the task of detecting hepatic metastases. METHODS: Datasets from contrast-enhanced CT scans of the liver were provided to participants in an NIH-, AAPM- and Mayo Clinic-sponsored Low Dose CT Grand Challenge. Training data included full-dose and quarter-dose scans of the ACR CT accreditation phantom and 10 patient examinations; both images and projections were provided in the training data. Projection data were supplied in a vendor-neutral standardized format (DICOM-CT-PD). Twenty quarter-dose patient datasets were provided to each participant for testing the performance of their technique. Images were provided to sites intending to perform denoising in the image domain. Fully preprocessed projection data and statistical noise maps were provided to sites intending to perform iterative reconstruction. Upon return of the denoised or iteratively reconstructed quarter-dose images, randomized, blinded evaluation of the cases was performed using a Latin Square study design by 11 senior radiology residents or fellows, who marked the locations of identified hepatic metastases. Markings were scored against reference locations of clinically or pathologically demonstrated metastases to determine a per-lesion normalized score and a per-case normalized score (a faculty abdominal radiologist established the reference location using clinical and pathological information). Scores increased for correct detections; scores decreased for missed or incorrect detections. The winner for the competition was the entry that produced the highest total score (mean of the per-lesion and per-case normalized score). Reader confidence was used to compute a Jackknife alternative free-response receiver operating characteristic (JAFROC) figure of merit, which was used for breaking ties. RESULTS: 103 participants from 90 sites and 26 countries registered to participate. Training data were shared with 77 sites that completed the data sharing agreements. Subsequently, 41 sites downloaded the 20 test cases, which included only the 25% dose data (CTDIvol = 3.0 ± 1.8 mGy, SSDE = 3.5 ± 1.3 mGy). 22 sites submitted results for evaluation. One site provided binary images and one site provided images with severe artifacts; cases from these sites were excluded from review and the participants removed from the challenge. The mean (range) per-lesion and per-case normalized scores were -24.2% (-75.8%, 3%) and 47% (10%, 70%), respectively. Compared to reader results for commercially reconstructed quarter-dose images with no noise reduction, 11 of the 20 sites showed a numeric improvement in the mean JAFROC figure of merit. Notably two sites performed comparably to the reader results for full-dose commercial images. The study was not designed for these comparisons, so wide confidence intervals surrounded these figures of merit and the results should be used only to motivate future testing. CONCLUSION: Infrastructure and methodology were developed to rapidly estimate observer performance for liver metastasis detection in low-dose CT examinations of the liver after either image-based denoising or iterative reconstruction. The results demonstrated large differences in detection and classification performance between noise reduction methods, although the majority of methods provided some improvement in performance relative to the commercial quarter-dose images with no noise reduction applied.

A comparison of relative proton stopping power measurements across patient size using dual- and single-energy CT.

PURPOSE: To evaluate the accuracy and precision across phantom size of a dual-energy computed tomography (DECT) technique used to calculate relative proton stopping power (SPR) in tissue-simulating materials and a silicone implant relative to conventional single-energy CT (SECT). MATERIAL AND METHODS: A 32 cm lateral diameter (CIRS model 062M, Norfolk, Virginia) electron density phantom containing inserts which simulated the chemical composition of eight tissues in a solid-water background was scanned using SECT and DECT. A liquid water insert was included to confirm CT number accuracy. All materials were also placed in four water tanks, ranging from 15 to 45 cm in lateral width and scanned using DECT and SECT. A silicone breast implant was scanned in the same water phantoms. SPR values were calculated based on commercial software (syngo CT Dual Energy, Siemens Healthcare GmbH) and compared to reference values derived from proton beam measurements. Accuracy and precision were quantified across phantom size using percent error and standard deviation. Graphical and regression analysis were used to determine whether SECT or DECT was superior in estimating SPR across phantom size. RESULTS: Both DECT and SECT SPR data resulted in good agreement with the reference values. Percent error was ±3% for both DECT and SECT in all materials except lung and dense bone. The coefficient of variation (CV) across materials and phantom sizes was 1.12% for SECT and 0.96% for DECT. Material-specific regression and graphical analysis did not reveal size dependence for either technique but did show reduced systematic bias with DECT for dense bone and liver. Mean percent error in SPR for the implant was reduced from 11.46% for SECT to 0.49% for DECT. CONCLUSIONS: We demonstrate the superior ability of DECT to mitigate systematic bias in bones and liver and estimate SPR in a silicone breast implant.

Application of Posterior Thigh Three-Dimensional Profunda Artery Perforator Perforasomes in Refining Next-Generation Flap Designs: Transverse, Vertical, and S-Shaped Profunda Artery Perforator Flaps.

BACKGROUND: This study aimed to delineate and compare the hot spots and three-dimensional vascular territories of dominant profunda artery perforators in the posterior thigh region, and modifications in flap design are discussed. METHODS: Twenty-nine posterior thigh flaps were raised in fresh cadaveric specimens, and profunda artery perforators were documented. Dominant perforators were injected with iodinated contrast to assess perforasomes using computed tomographic angiography. Analysis with three-dimensional rendering and volume calculations of perfusion patterns was performed. RESULTS: In total, 316 perforators were mapped and 33 perforators were injected for analysis. The hot spot for dominant perforators was the proximal medial quadrant, 5 to 10 cm from the inferior gluteal crease, with two smaller hot spots in the upper lateral and distal posterior midline. Although 69 percent were musculocutaneous, distal perforators were predominantly septocutaneous in the posterior midline, 5 to 8 cm from the popliteal crease. Proximal perforators were classified into first (most proximal) and second perforators, and their median perforasome was 233 and 286.4 cm, respectively (p = 0.86). There were no significant differences between proximal and distal perforators in perforasome surface areas, percentage areas perfused, and perforasome volumes. Large linking vessel networks were attributed to a broader perforasome and greater overlap between adjacent or distal perforators. CONCLUSIONS: Dominant linking vessels and recurrent flow through the subdermal plexus contribute to the robust vascular supply of profunda artery perforator flaps. Posterior thigh region perforator hot spots and their perfusion characteristics can inform the potential limits, orientation, and modifications of flap or skin paddle designs.

Three-Dimensional Computed Tomographic Angiography Study of the Interperforator Flow of the Lower Leg.

BACKGROUND: The area perfused by a single perforator depends on its perforasome and its unique interperforator flow pattern. The purpose of this study was to clarify the interperforator flow patterns of the peroneal and posterior tibial artery perforators using three-dimensional computed tomographic angiography. METHODS: Thirteen whole-leg skin flaps were harvested in the subfascial plane from fresh cadavers. Peroneal, posterior tibial, anterior tibial, and sural artery perforators with a diameter greater than 0.5 mm were documented. Three-dimensional computed tomographic angiography with an injection of iodinated contrast medium into the peroneal or posterior tibial artery perforator was used to investigate the percentages of the area and the perforators that were perfused. RESULTS: The mean percentage of the total area perfused was as follows: peroneal artery perforator, 42.0 percent; posterior tibial artery perforator, 38.0 percent (p = 0.084). The mean percentage of the total perforators perfused was as follows: peroneal artery perforator, 55.0 percent; posterior tibial artery perforator, 44.2 percent (p = 0.004). Although the mean percentages of same-source artery perforators perfused by a peroneal artery perforator (73.6 percent) and by a posterior tibial artery perforator (77.2 percent) did not differ (p = 0.513), the mean percentages of other-source artery perforators perfused by a peroneal artery perforator (49.9 percent) and by a posterior tibial artery perforator (32.3 percent) were significantly different (p < 0.001). CONCLUSIONS: This study demonstrated that a single peroneal or posterior tibial artery perforator perfused approximately 40 percent of the whole leg surface and that peroneal and posterior tibial artery perforators had different interperforator flow patterns. The results of this study may improve preoperative planning for pedicled perforator flap surgery. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Selective use of cardiac computed tomography angiography: an alternative diagnostic modality before second-stage single ventricle palliation.

OBJECTIVES: To assess the accuracy and risk of substituting cardiac computed tomography for cardiac catheterization in select patients for evaluation of anatomy before second-stage single ventricle palliation. METHODS: This is a retrospective review of consecutive diagnostic cardiac catheterization (n=16) and computed tomography studies (n=16) performed before second-stage single ventricle palliation from March 2010 to July 2012 at a single institution. Risk (anesthesia, vascular access, contrast, and radiation exposure), accuracy, and postoperative course were compared. Nonparametric analysis was used to compare differences in group medians. RESULTS: General anesthesia was used for 16 of 16 cardiac catheterization studies and 1 of 16 computed tomography studies. Vascular access was central venous and/or arterial for all cardiac catheterization studies and a peripheral intravenous line for all computed tomography studies. Median age- and size-adjusted radiation dose was 14.0 mSv for cardiac catheterization and 1.1 mSv for computed tomography. Contrast dose was 4.8 mL/kg for the cardiac catheterization group and 2 mL/kg for the computed tomography group. There were no computed tomography discrepancies and 1 discrepancy between cardiac catheterization and surgical findings. There were 8 adverse events in 6 patients in the cardiac catheterization group and 1 adverse event in the computed tomography group. There was no difference between groups in postoperative course or need for repeat intervention. CONCLUSIONS: Cardiac computed tomography and cardiac catheterization are equally accurate for evaluation of anatomy before second-stage single ventricle palliation when compared with surgical findings. Computed tomography may be the preferred test in select patients because of decreased vascular access and anesthesia risk, lower radiation and contrast exposure, and fewer adverse events.

Reducing image noise in computed tomography (CT) colonography: effect of an integrated circuit CT detector.

OBJECTIVE: To investigate whether the integrated circuit (IC) detector results in reduced noise in computed tomography (CT) colonography (CTC). METHODS: Three hundred sixty-six consecutive patients underwent clinically indicated CTC using the same CT scanner system, except for a difference in CT detectors (IC or conventional). Image noise, patient size, and scanner radiation output (volume CT dose index) were quantitatively compared between patient cohorts using each detector system, with separate comparisons for the abdomen and pelvis. RESULTS: For the abdomen and pelvis, despite significantly larger patient sizes in the IC detector cohort (both P < 0.001), image noise was significantly lower (both P < 0.001), whereas volume CT dose index was unchanged (both P > 0.18). Based on the observed image noise reduction, radiation dose could alternatively be reduced by approximately 20% to result in similar levels of image noise. CONCLUSION: Computed tomography colonography images acquired using the IC detector had significantly lower noise than images acquired using the conventional detector. This noise reduction can permit further radiation dose reduction in CTC.

Three-wavelength murine photoplethysmography for estimation of vascular gold nanorod concentration.

Nanoparticle-assisted photo-thermal (NAPT) ablation has become a new and attractive modality for the treatment of cancerous tumors. This therapy exploits the passive accumulation of intravenously delivered optically resonant metal nanoparticles into tumors, however, the circulating bioavailability of these particles is often unknown. We present a non-invasive optical device capable of monitoring the circulation of optically resonant gold nanorods. The device, referred to as a pulse photometer, uses the technique of multi-wavelength photoplethysmography. We simultaneously report the circulation of gold nanorods and oximetry for six hours post-injection in mice with no anesthesia and remove the probe when not collecting data. The instrument shows good agreement (R(2) = 0.903, n = 30) with ex vivo spectrophotometric analysis of blood samples. The real-time feedback provided has a strong potential for reducing variability and thus improving the efficacy of similar clinical therapies.

Murine photoplethysmography for in vivo estimation of vascular gold nanoshell concentration.

There is an urgent clinical need to monitor the intravenous delivery and bioavailability of circulating nanoparticles used in cancer therapy. This work presents the use of photoplethysmography for the noninvasive real-time estimation of vascular gold nanoshell concentration in a murine subject. We develop a pulse photometer capable of accurately measuring the photoplethysmogram in mice and determining the ratio of pulsatile changes in optical extinction between 805 and 940 nm, commonly referred to as R. These wavelengths are selected to correspond to the extinction properties of gold nanoshells. Six 30-s measurements (5 min, 2, 4, 6, 8, 10 h) are taken under light anesthesia to observe the change in R as the nanoparticles clear from the circulation. Our model describes the linear fit (R(2)=0.85) between R and the concentration of nanoparticles measured via ex vivo spectrophotometric and instrumental neutron activation analysis. This demonstrates the utility of this technique in support of clinical nanoparticle therapies.