Canine preclinical safety evaluation of a multimodal nanoparticle agent (Nanotrast-CF800) for image-guided cancer surgery.

Surgical oncology often requires the use of contrast-enhanced cross-sectional imaging preoperatively to characterize solitary tumours and identify sentinel lymph nodes. Intraoperative optical guidance can effectively aid tissue-sparing tumour excision and locate sentinel lymph nodes. Nanotrast-CF800 (CF800) is a novel dual-modality contrast agent, which co-encapsulates iohexol and indocyanine green (ICG) within a liposomal nanoparticle. It was developed for preoperative and intraoperative imaging of solitary tumours and sentinel lymph node mapping and its efficacy has been demonstrated in preclinical animal models (Zheng et al. 2015). The objective of this study is to evaluate the safety profile of CF800 following intravenous administration in healthy dogs. Six research dogs were randomized into two groups. Group 1 received a low dose (1 mL/kg) and group 2 received a high dose (5 mL/kg). Dogs were placed under general anesthesia and a continuous rate infusion of CF800 was administered based on group allocation. Physiologic parameters including heart rate, respiratory rate, direct arterial blood pressure, cardiac output, and temperature were measured at set time points. Plasma concentrations of iohexol, ICG, and histamine were measured at set time points. Dogs underwent whole body computed tomography scans pre-injection, 2-, and 7-days post-injection (p.i.). Contrast enhancement was measured in select organ systems and great vessels at each time point. There were no significant changes in physiologic parameters following IV infusion of CF800 in all dogs. Plasma iohexol and ICG concentrations peaked at 1 day p.i., while histamine concentrations peaked at 30 minutes p.i. Significant contrast enhancement was noted within the liver, heart, aorta, and caudal vena cava on day 2 p.i., which was significantly different compared to baseline. Prolonged contrast retention within the liver was identified. Intravenous administration of CF800 was safe to use in healthy dogs with no significant systemic adverse effects.

Comparison of estimated GFR using cystatin C versus creatinine in pediatric kidney transplant recipients.

BACKGROUND: An accurate, rapid estimate of glomerular filtration rate (GFR) in kidney transplant patients affords early detection of transplant deterioration and timely intervention. This study compared the performance of serum creatinine (Cr) and cystatin C (CysC)-based GFR equations to measured GFR (mGFR) using iohexol among pediatric kidney transplant recipients. METHODS: CysC, Cr, and mGFR were obtained from 45 kidney transplant patients, 1-18 years old. Cr- and CysC-estimated GFR (eGFR) was compared against mGFR using the Cr-based (Bedside Schwartz, U25-Cr), CysC-based (Gentian CysC, CAPA, U25-CysC), and Cr-CysC combination (CKiD Cr-CysC, U25 Cr-CysC) equations in terms of bias, precision, and accuracy. Bland-Altman plots assessed the agreement between eGFR and mGFR. Secondary analyses evaluated the formulas in patients with biopsy-proven histological changes, and K/DOQI CKD staging. RESULTS: Bias was small with Gentian CysC (0.1 ml/min/1.73 m2); 88.9% and 37.8% of U25-CysC estimations were within 30% and 10% of mGFR, respectively. In subjects with histological changes on biopsy, Gentian CysC had a small bias and U25-CysC were more accurate-both with 83.3% of and 41.7% of estimates within 30% and 10% mGFR, respectively. Precision was better with U25-CysC, CKiD Cr-CysC, and U25 Cr-CysC. Bland-Altman plots showed the Bedside Schwartz, Gentian CysC, CAPA, and U25-CysC tend to overestimate GFR when > 100 ml/min/1.72 m2. CAPA misclassified CKD stage the least (whole cohort 24.4%, histological changes on biopsy 33.3%). CONCLUSIONS: In this small cohort, CysC-based equations with or without Cr may have better bias, precision, and accuracy in predicting GFR.

Impact of humanized vancomycin infusion on kidney function and kidney injury in a translational rat model.

Allometric dose scaling aims to create isometric exposures between animals and humans and is often employed in preclinical pharmacokinetic/pharmacodynamic models. Bolus-administration with allometric scaling is the most simple and commonly used strategy in pre-clinical kidney injury studies; however, it is possible to humanize drug exposures. Currently, it is unknown if dose-matched, bolus-administration with allometric scaling results in similar outcomes compared to humanized infusions in the vancomycin induced kidney injury model. We utilized a preclinical Sprague-Dawley rat model to compare traditional allometrically-scaled, dose-matched, bolus-administration of vancomycin to an infusion-pump controlled, humanized infusion scheme to assess for differences in iohexol-measured kidney function and urinary kidney injury biomarkers. Following 24 h of vancomycin administration, rats in the humanized infusion group had equivalent area under the curve exposures to animals in the dose-matched bolus group (93.7 mg·h/L [IQR 90.2-97.2] vs. 99.5 mg·h/L [IQR 95.1-104.0], P = 0.07). No significant differences in iohexol-measured kidney function nor meaningful differences in urinary kidney injury biomarkers, kidney injury molecule-1, clusterin, and osteopontin, were detected. Administration of intravenous vancomycin as either a humanized infusion or dose-matched bolus resulted in similar vancomycin exposures. No differences in iohexol-measured GFR nor meaningful differences in urinary kidney injury biomarkers were observed among male Sprague-Dawley rats.

Metabolomic Study on Iohexol-Induced Nephrotoxicity in Rats Based on NMR and LC-MS Analyses.

Iohexol, the raw material of nonionic X-ray computed tomography (X-CT) contrast medium, is usually injected into the vein before CT angiography diagnosis. It is used for angiography, urography, and lymphography. With the advantages of low contrast density and good tolerance, it is currently one of the most popular contrast media. However, the renal toxicity of iohexol seriously affects its safety use. Therefore, it is of great importance to identify new potential diagnostic biomarkers and therapeutic targets in the process of contrast medium-induced acute kidney injury (CI-AKI) in order to safely use iohexol in clinical practice. In this study, in order to understand the metabolic mechanism of CI-AKI, ultra-high-performance liquid chromatography/quadrupole-Orbitrap-mass spectrometry and 1H NMR-based metabolomic techniques were utilized to study the metabolic spectra of kidney, plasma, and urine from CI-AKI rats, and a total of 30 metabolites that were closely related to kidney injury were screened out, which were mainly related to 9 metabolic pathways. The results further indicated that iohexol might intensify kidney dysfunction in vivo by disrupting the metabolic pathways in the body, especially through blocking energy metabolism, amino acid metabolism, and promoting inflammatory reactions.

Evaluating suspected small bowel obstruction with the water-soluble contrast challenge.

With optimized technique, the water-soluble contrast challenge is effective at triaging patients for operative vs non-operative management of suspected small bowel obstruction. Standardized study structure and interpretation guidelines aid in clinical efficacy and ease of use. Many tips and tricks exist regarding technique and interpretation, and their understanding may assist the interpreting radiologist. In the future, a CT-based water-soluble contrast challenge, utilizing oral contrast given as part of the initial CT examination, might allow for a more streamlined algorithm and provide more rapid results.

Accuracy of single intravenous access iohexol GFR in children is hampered by marker contamination.

Measurement of glomerular filtration rate (GFR) in children by iohexol injection and blood sampling from the contralateral arm is widely used. A single intravenous access for iohexol injection and subsequent blood sampling has the obvious advantages of being less painful and easier to perform. The purpose of our study was to determine if blood samples drawn from the injection access are feasible and accurate for iohexol GFR (iGFR) measurements. Thirty-one children, median age 10.5 (range 6-17) years, with chronic kidney disease were given a bolus of iohexol followed by extended saline flushing and subsequent venous blood samples collected from the injection access as well as from a cannula in the contralateral arm, the latter serving as the reference method. Paired venous blood samples were collected at four time points (2, 3, 3.5 and 4 h) after the iohexol bolus. Blood sample discarding preceded and saline flushing followed each blood sampling to avoid marker contamination. iGFR based on samples drawn from the injection access at 2 and 3 h showed significantly lower iGFR than measurement from the contralateral arm (p < 0.01). Singlepoint iGFR did not differ significantly after 3-4 repeated procedures of blood discarding and saline flusing (3.5 and 4 h). Despite thorough saline flushing there is still a relatively high risk of falsely low iGFR due to marker contamination in blood samples from the injection site. Hence, blood sampling from a second intravenous access is recommended for routine iohexol GFR measurements in children.Clinical trial registration: ClinicalTrials.gov, Identifier NCT01092260, https://clinicaltrials.gov/ct2/show/NCT01092260?term=tondel&rank=2 .

A practical biphasic contrast media injection protocol strongly enhances the aorta and pulmonary artery simultaneously using a single CT angiography scan.

BACKGROUND: Enhancement profiles of the pulmonary artery (PA) and aorta differ when using computed tomography (CT) angiography. Our aim was to determine the optimal CT protocol for a one-time CT scan that assesses both blood vessels. METHODS: We prospectively enrolled 101 cases of CT angiography in patients with suspected pulmonary embolism or aortic dissection from our center between 2018 and 2020. We also retrospectively collected the data of 40 patients who underwent traditional two-time CT scans between 2015 and 2018. Patients were divided into four groups: test bolus (TB) I, TB II, bolus-tracking (BT) I, and BT II. The enhancement of the PA and aorta, and the radiation doses used in the four groups were collected. Those who underwent two-time scans were classified into the traditional PA or aorta scan groups. Data were compared between the BT and traditional groups. RESULTS: The aortic enhancement was highest in BT II (294.78 ± 64.48 HU) followed BT I (285.18 ± 64.99 HU), TB II (186.58 ± 57.53 HU), and TB I (173.62 ± 69.70 HU). The radiation dose used was lowest in BT I (11.85 ± 5.55 mSv) and BT II (9.07 ± 3.44 mSv) compared with that used in the traditional groups (20.07 ± 7.78 mSv) and accounted for half of the traditional group (45.17-59.02%). The aortic enhancement was also highest in BT II (294.78 ± 64.48 HU) followed by BT I (285.18 ± 64.99 HU) when compared with that in the traditional aorta scan group (234.95 ± 94.18 HU). CONCLUSION: Our CT protocol with a BT technique allows for a lower radiation dose and better image quality of the PA and aorta than those obtained using traditional CT scans. TRIAL REGISTRATION: NCT04832633, retrospectively registered in April 2021 to the clinical trial registry.

Kinetic Glomerular Filtration Rate Equations in Patients With Shock: Comparison With the Iohexol-Based Gold-Standard Method.

OBJECTIVES: Static glomerular filtration rate formulas are not suitable for critically ill patients because of nonsteady state glomerular filtration rate and variation in the volume of distribution. Kinetic glomerular filtration rate formulas remain to be evaluated against a gold standard. We assessed the most accurate kinetic glomerular filtration rate formula as compared to iohexol clearance among patients with shock. DESIGN: Retrospective multicentric study. SETTING: Three French ICUs in tertiary teaching hospitals. PATIENTS: Fifty-seven patients within the first 12 hours of shock. MEASUREMENTS AND MAIN RESULTS: On day 1, we compared kinetic glomerular filtration rate formulas with iohexol clearance, with or without creatinine concentration correction according to changes in volume of distribution and ideal body weight. We analyzed three static glomerular filtration rate formulas (Cockcroft and Gault, modification of diet in renal disease, and Chronic Kidney Disease-Epidemiology Collaboration), urinary creatinine clearance, and seven kinetic glomerular filtration rate formulas (Jelliffe, Chen, Chiou and Hsu, Moran and Myers, Yashiro, Seelhammer, and Brater). We evaluated 33 variants of these formulas after applying corrective factors. The bias ranged from 12 to 47 mL/min/1.73 m2. Only the Yashiro equation had a lower bias than urinary creatinine clearance before applying corrective factors (15 vs 20 mL/min/1.73 m2). The corrected Moran and Myers formula had the best mean bias, 12 mL/min/1.73 m2, but wide limits of agreement (-50 to 73). The corrected Moran and Myers value was within 30% of iohexol-clearance-measured glomerular filtration rate for 27 patients (47.4%) and was within 10% for nine patients (15.8%); other formulas showed even worse accuracy. CONCLUSIONS: Kinetic glomerular filtration rate equations are not accurate enough for glomerular filtration rate estimation in the first hours of shock, when glomerular filtration rate is greatly decreased. They can both under- or overestimate glomerular filtration rate, with a trend to overestimation. Applying corrective factors to creatinine concentration or volume of distribution did not improve accuracy sufficiently to make these formulas reliable. Clinicians should not use kinetic glomerular filtration rate equations to estimate glomerular filtration rate in patients with shock.

A systematic review of cost-effectiveness analyses across the acute kidney injury landscape.

Introduction: Acute kidney injury (AKI) is a complex and common condition associated with increased morbidity, mortality, and costs. Evidence from cost-effectiveness analysis (CEA) have targeted various aspects of AKI including detection with biomarkers, treatment with renal replacement therapy, and prevention when using contrast media. However, there has not been a systematic review of these studies across the entirety of AKI.Areas covered: PubMed, Embase, and Cochrane library were used to identify CEA studies that involved AKI from 2004 onwards. These studies compared AKI treatment through renal replacement therapies (n = 6), prevention of contrast-induced-AKI (CI-AKI) using different media (n = 3), and diagnosis with novel biomarkers (n = 2). Treatment strategies for AKI focused on continuous versus intermittent renal replacement therapy. While there was no consensus, the majority of studies favored the continuous form. For contrast media, both studies found iodixanol to be cost-effective compared to iohexol for preventing CI-AKI. Additionally, novel biomarkers showed potential to be cost-effective in risk assessment and detection of AKI.Expert opinion: Consistent criteria such as a lifetime time horizon would allow for better model comparisons. Further research on clinical parameters to capture transition probabilities between stages within AKI and progression to downstream kidney disease is needed.

Combined rare anatomic variants: persistent primitive olfactory artery and azygos pericallosal artery.

The persisting primitive olfactory artery (PPOA) is a rare anatomic variation of the anterior cerebral artery (ACA), being encountered in less than 1% of cases. Different morphological types were reported previously. In type 3, only once reported previously, the PPOA gives off two branches, a nasal one which courses in the olfactory sulcus to supply the territory of the anterior ethmoidal artery, and the callosomarginal artery. It is reported here a combination of rare anatomic variants found in a 71-year-old male patient investigated by computed tomography angiography. A left PPOA left the A1 segment of the ACA and was classified as subtype 3b, as its branches were the nasal one and a frontal trunk, not the callosomarginal artery. That PPOA had a characteristic hairpin turn applied on the anterior fossa floor. The ACA continued as azygos pericallosal artery, which is also a rare finding. As the nasal branch of the PPOA and its hairpin turn is closely related to the anterior fossa floor, such variant should be carefully documented when combined approaches of the skull base are planned by rhinologists and neurosurgeons.

The feasibility of low iodine dynamic CT angiography with test bolus for evaluation of lower extremity peripheral artery disease.

OBJECTIVE: This study aims to determine if low iodine dynamic computed tomography angiography performed after a fixed delay or test bolus acquisition demonstrates high concordance with clinical computed tomography angiography (using a routine amount of iodinated contrast) to display lower extremity peripheral arterial disease. METHODS: After informed consent, low iodine dynamic computed tomography angiography examination (using either a fixed delay or test bolus) using 50 ml of iodine contrast media was performed. A subsequent clinical computed tomography angiography using standard iodine dose (115 or 145 ml) served as the reference standard. A vascular radiologist reviewed dynamic and clinical computed tomography angiography images to categorize the lumen into "not opacified", "<50% stenosis", " 50 ̶70% stenosis", ">70% stenosis", and "occluded" for seven arterial segments in each lower extremity. Concordance between low iodine dynamic computed tomography angiography and the routine iodine reference standard was calculated. The clinical utility of 4D volume-rendered images was also evaluated. RESULTS: Sixty-eight patients (average age 66.1 ± 12.3 years, male; female = 49: 19) were enrolled, with 34 patients each undergoing low iodine dynamic computed tomography angiography using fixed delay and test bolus techniques, respectively. One patient assigned to the test bolus group did not undergo low iodine computed tomography angiography due to unavailable delayed time. The fixed delay was 13 s, with test bolus acquisition resulting in a mean variable delay prior to image acquisition of 19.5 s (range; 8-32 s). Run-off to the ankle was observed using low iodine dynamic computed tomography angiography following fixed delay and test bolus acquisition in 76.4% (26/34) and 100% (33/33) of patients, respectively (p = 0.005). Considering extremities with run-off to the ankle and without severe artifact, the concordance rate between low iodine dynamic computed tomography angiography and the routine iodine reference standard was 86.8% (310/357) using fixed delay and 97.9% (425/434) using test bolus (p < 0.001). 4D volume-rendered images using fixed delay and test bolus demonstrated asymmetric flow in 57.7% (15/26) and 58.1% (18/31) (p = 0.978) of patients, and collateral blood flow in 11.5% (3/26) and 22.6% (7/31) of patients (p = 0.319), respectively. CONCLUSION: Low iodine dynamic computed tomography angiography with test bolus acquisition has a high concordance with routine peripheral computed tomography angiography performed with standard iodine dose, resulting in improved run-off to the ankle compared to dynamic computed tomography angiography performed after a fixed delay. This method is useful for minimizing iodine dose in patients at risk for contrast-induced nephropathy. 4D volume-rendered computed tomography angiography images provide useful dynamic information.

Iodine-related attenuation in contrast-enhanced dual-energy computed tomography in small-sized solid-type lung cancers is associated with the postoperative prognosis.

BACKGROUND: To investigate the correlation between iodine-related attenuation in contrast-enhanced dual-energy computed tomography (DE-CT) and the postoperative prognosis of surgically resected solid-type small-sized lung cancers. METHODS: We retrospectively reviewed the DE-CT findings and postoperative course of solid-type lung cancers ≤3 cm in diameter. After injection of iodinated contrast media, arterial phases were scanned using 140-kVp and 80-kVp tube voltages. Three-dimensional iodine-related attenuation (3D-IRA) of primary tumors at the arterial phase was computed using the "lung nodule" application software. The corrected 3D-IRA normalized to the patient's body weight and contrast medium concentration was then calculated. RESULTS: A total of 120 resected solid-type lung cancers ≤3 cm in diameter were selected for analysis (82 males and 38 females; mean age, 67 years). During the observation period (median, 47 months), 32 patients showed postoperative recurrence. Recurrent tumors had significantly lower 3D-IRA and corrected 3D-IRA at early phase compared to non-recurrent tumors (p = 0.046 and p = 0.027, respectively). The area under the receiver operating characteristic curve for postoperative recurrence was 0.624 for the corrected 3D-IRA at early phase (p = 0.025), and the cutoff value was 5.88. Kaplan-Meier curves for disease-free survival indicated that patients showing tumors with 3D-IRA > 5.88 had a significantly better prognosis than those with tumors showing 3D-IRA < 5.88 (p = 0.017). CONCLUSIONS: The 3D-IRA of small-sized solid-type lung cancers on contrast-enhanced DE-CT was significantly associated with postoperative prognosis, and low 3D-IRA tumors showed a higher TNM stage and a significantly poorer prognosis.

Anatomic variations of the superficial temporal artery.

The superficial temporal artery (STA) is a terminal branch of the external carotid artery. It is commonly described as coursing posterior to the mandibular condyle and over the posterior zygomatic root (PZR) and then dividing terminally into parietal and frontal branches. However, possible variations of the main trunk of the STA have seemingly been overlooked. This study retrospectively examined the archived head tomography angiograms of 43 patients to determine the morphology and topography of the STA prior to its terminal bifurcation. In 79% of patients, the STA topography related to the mandibular condyle was bilaterally symmetrical, either retrocondylar (65.1%) or laterocondylar (13.6%). The parietal branch was sometimes absent unilaterally (16.3%) or bilaterally (9.3%). In 2/43 cases, the frontal branch of the STA was unilaterally absent. When both terminal branches were present, the bifurcation was retrocondylar or immediately above the PZR when on the PZR, or the terminal division of the STA was high above the PZR. In 88.4% of the STAs, different patterns of kinking and coiling were documented, including retrocondylar kinks (27.9%), laterocondylar kinks (20.9%), kinks placed on the PZR (81.4%) and variably oriented suprazygomatic kinks (32.6%). Five of the 86 STAs were coiled, one retrocondylar, one laterocondylar, and three other placed on the PZR. Two cases showed unilateral pseudoaneurysms of the STA, one above the PZR and the other on the temporomandibular joint. The STA is surgically important; therefore, the number of anatomical studies of the STA should increase.

Case Report and Literature Review on Low-Osmolar, Non-Ionic Iodine-Based Contrast-Induced Encephalopathy.

Contrast-induced encephalopathy (CIE) is a rare complication following percutaneous carotid and coronary interventions, and important diagnostic radiological signs include brain edema and cortical enhancement. In this report, we detail a case of probable CIE in an 84-year-old woman following a normal diagnostic coronary angiography (CAG) that involved 20 mL of the low-osmolar, non-ionic monomeric, iodine-based contrast agent iopromide (Ultravist 370). The patient was unconscious and presented with hemiparesis, hemianopia, recurrent seizures, and cardiac and respiratory arrest within minutes to hours following the procedure. Non-contrast computed tomography (CT) of the head showed increased subarachnoid density, cortical enhancement, and brain edema in the right hemisphere. Three days of rehydration, reduction in cranial pressure, and treatment with an anticonvulsant and dexamethasone resulted in a gradual recovery with no neurological deficits. This case highlights that severe neurotoxic symptoms may occur in response to low doses of low-osmolar, non-ionic, monomeric contrast agents. This finding is of importance to interventional cardiologists for diagnostic considerations and development of treatment plans.

Intrathecal iodinated contrast-induced transient spinal shock.

Transient spinal shock is a previously unreported complication of intrathecal contrast. A 63-year-old man presented with the chief complaint of worsening back pain. Computed topography of lumbar spine without contrast showed a lytic lesion. After international normalized ratio (INR) correction, patient was sent for CT myelogram. After intrathecal contrast injection, the patient dropped his blood pressure profoundly and developed clinical manifestations of spinal shock. Emergent intravenous bolus fluids were initiated resulting in improvement in blood pressure. Patient's spinal shock resolved within hours. CT myelogram was normal except previously known lytic lesion. It was concluded that the transient shock was most likely due to contrast injection. We believe that this is the first reported case of transient spinal shock following CT myelogram using water-soluble iodinated non-ionic contrast agent administered intrathecally.

Mandibular nerve block in juvenile Nile crocodile: a cadaveric study.

OBJECTIVE: To develop a technique for performing the mandibular nerve block in Nile crocodiles. STUDY DESIGN: Experimental cadaveric study. ANIMALS: A total of 16 juvenile Nile crocodile heads. METHODS: To study the course of the mandibular nerve, one head was dissected. Computed tomography (CT) examination was performed in two heads to identify useful landmarks. Thereafter, a hypodermic needle was inserted through the external mandibular fenestra of 17 hemimandibles (13 heads), and a mixture of methylene blue and iohexol was injected. Injection volumes were 0.5 (n = 7) and 1.0 mL (n = 10) for hemimandibles < 15 and ≥ 15 cm long, respectively. Iohexol spread and nerve staining with methylene blue were assessed with CT and anatomical dissection, respectively. Data were analysed with one-sample t test or Mann-Whitney U test. Significance was set at p < 0.05. RESULTS: Both anatomical dissection and imaging confirmed the external mandibular fenestra as a useful anatomical landmark for needle insertion. The CT images acquired after needle positioning confirmed that its tip was located on the medial bony mandibular surface formed by the fusion of the angular and coronoid bones in 100% cases. In all the hemimandibles, the rostrocaudal spread of contrast was > 23 mm. The length of the stained mandibular nerve in the temporal region and of the stained medial branch of the mandibular nerve, as well as the dorsoventral and mediolateral spread of iohexol, was greater in group 1.0 than in group 0.5 (p < 0.001). The caudal spread of iohexol was greater in group 1.0 than in group 0.5 (p = 0.01). CONCLUSIONS AND CLINICAL RELEVANCE: The technique developed in this study is feasible. Both injection volumes resulted in staining of the mandibular nerve. The spread of contrast in the anatomical region of interest may result in successful sensory block.

Impact of iodine concentration and scan parameters on image quality, contrast enhancement and radiation dose in thoracic CT.

BACKGROUND: We investigated the impact of varying contrast medium (CM) densities and x-ray tube potentials on contrast enhancement (CE), image quality and radiation dose in thoracic computed tomography (CT) using two different scanning techniques. METHODS: Seven plastic tubes containing seven different CM densities ranging from of 0 to 600 HU were positioned inside a commercial chest phantom with padding, representing three different patient sizes. Helical scans of the phantom in single-source mode were obtained with varying tube potentials from 70 to 140 kVp. A constant volume CT dose index (CTDIvol) depending on phantom size and automatic dose modulation was tested. CE (HU) and image quality (contrast-to-noise ratio, CNR) were measured for all combinations of CM density and tube potential. A reference threshold of CE and kVp was defined as ≥ 200 HU and 120 kVp. RESULTS: For the medium-sized phantom, with a specific CE of 100-600 HU, the diagnostic CE (200 HU) at 70 kVp was ~ 90% higher than at 120 kVp, for both scan techniques (p < 0.001). Changes in CM density/specific HU together with lower kVp resulted in significantly higher CE and CNR (p < 0.001). When changing only the kVp, no statistically significant differences were observed in CE or CNR (p ≥ 0.094), using both dose modulation and constant CTDIvol. CONCLUSIONS: For thoracic CT, diagnostic CE (≥ 200 HU) and maintained CNR were achieved by using lower CM density in combination with lower tube potential (< 120 kVp), independently of phantom size.

Evaluation of the pharmacokinetic drug-drug interaction potential of iohexol, a renal filtration marker.

PURPOSE: Carboplatin dose is calculated based on kidney function, commonly estimated with imperfect creatinine-based formulae. Iohexol is used to measure glomerular filtration rate (GFR) and allows calculation of a more appropriate carboplatin dose. To address potential concerns that iohexol administered during a course of chemotherapy impacts that therapy, we performed in vitro and in vivo pharmacokinetic drug-drug interaction evaluations of iohexol. METHODS: Carboplatin was administered IV to female mice at 60 mg/kg with or without iohexol at 300 mg/kg. Plasma ultrafiltrate, kidney and bone marrow platinum was quantitated by atomic absorption spectrophotometry. Paclitaxel microsomal and gemcitabine cytosolic metabolism as well as metabolism of CYP and UGT probes was assessed with and without iohexol at 300 µg/mL by LC-MS/MS. RESULTS: In vivo carboplatin exposure was not significantly affected by iohexol co-administration (platinum AUC combination vs alone: plasma ultrafiltrate 1,791 vs 1920 µg/mL min; kidney 8367 vs 9757 µg/g min; bone marrow 12.7 vs 12.7 µg/mg-protein min). Paclitaxel microsomal metabolism was not impacted (combination vs alone: 6-α-OH-paclitaxel 38.3 versus 39.4 ng/mL/60 min; 3-p-OH-paclitaxel 26.2 versus 27.7 ng/mL/60 min). Gemcitabine human cytosolic elimination was not impacted (AUC combination vs gemcitabine alone: dFdU 24.1 versus 23.7 µg/mL/30 min). Iohexol displayed no relevant inhibition of the CYP and UGT enzymes in human liver microsomes. CONCLUSIONS: Iohexol is unlikely to affect the clinical pharmacokinetics of carboplatin, paclitaxel, gemcitabine, or other agents used in combination with carboplatin treatment. Measuring GFR with iohexol to better dose carboplatin is unlikely to alter the safety or efficacy of chemotherapy through pharmacokinetic drug-drug interactions.

Split-bolus CT urography with synchronous nephrographic and excretory phase in dogs: comparison of image quality with three-phase CT urography and optimal allocation ratio of contrast medium.

BACKGROUND: Computed tomography urography (CTU), based on the excretion of contrast medium after its injection, allows visualization of the renal parenchyma and the renal collecting system. OBJECTIVES: To determine the optimal contrast medium dose allocation ratio to apply in split-bolus CTU in dogs. METHODS: This prospective, experimental, exploratory study used 8 beagles. In 3-phase CTU, unenhanced-, nephrographic-, and excretory-phase images were obtained with a single injection of 600 mg iodine/kg iohexol. In split-bolus CTU, two different contrast medium allocation ratios (30% and 70% for split CTU 1; 50% and 50% for split CTU 2) were used. Unenhanced phase image and a synchronous nephrographic-excretory phase image were acquired. RESULTS: Although the attenuation of the renal parenchyma was significantly lower when using both split CTUs than the 3-phase CTU, based on qualitative evaluation, the visualization score of the renal parenchyma of split CTU 1 was as high as that of the 3-phase CTU, whereas the split CTU 2 score was significantly lower than those of the two others. Artifacts were not apparent, regardless of CTU protocol. The diameter and opacification of the ureter in both split CTUs were not significantly different from those using 3-phase CTU. CONCLUSIONS: Split-bolus CTU with a contrast medium allocation ratio of 30% and 70% is feasible for evaluating the urinary system and allows sufficient enhancement of the renal parenchyma and appropriate distention and opacification of the ureter, with similar image quality to 3-phase CTU in healthy dogs. Split-bolus CTU has the advantages of reducing radiation exposure and the number of CT images needed for interpretation.