Assessment of iodine uptake by pancreatic cancer following chemotherapy using dual-energy CT.

Pancreatic cancer remains a major health problem, and only less than 20% of patients have resectable disease at the time of initial diagnosis. Systemic chemotherapy is often used in the patients with borderline resectable, locally advanced unresectable disease and metastatic disease. CT is often used to assess for therapeutic response; however, conventional imaging including CT may not correctly reflect treatment response after chemotherapy. Dual-energy (DE) CT can acquire datasets at two different photon spectra in a single CT acquisition, and permits separating materials and extract iodine by applying a material decomposition algorithm. Quantitative iodine mapping may have an added value over conventional CT imaging for monitoring the treatment effects in patients with pancreatic cancer and potentially serve as a unique biomarker for treatment response. In this pictorial essay, we will review the technique for iodine quantification of pancreatic cancer by DECT and discuss our observations of iodine quantification at baseline and after systemic chemotherapy with conventional cytotoxic agents, and illustrate example cases.

Bioresponsive and fluorescent hyaluronic acid-iodixanol nanogels for targeted X-ray computed tomography imaging and chemotherapy of breast tumors.

Nanotheranostics is a rapidly growing field combining disease diagnosis and therapy, which ultimately may add in the development of 'personalized medicine'. Here, we designed and developed bioresponsive and fluorescent hyaluronic acid-iodixanol nanogels (HAI-NGs) for targeted X-ray computed tomography (CT) imaging and chemotherapy of MCF-7 human breast tumors. HAI-NGs were obtained with a small size of ca. 90nm, bright green fluoresence and high serum stability from hyaluronic acid-cystamine-tetrazole and reductively degradable polyiodixanol-methacrylate via nanoprecipitation and a photo-click crosslinking reaction. Notably, paclitaxel (PTX)-loaded HAI-NGs showed a fast glutathione-responsive drug release. Confocal microscopy displayed efficient uptake of HAI-NGs by CD44 overexpressing MCF-7 cells via a receptor-mediated mechanism. MTT assays revealed that HAI-NGs were nontoxic to MCF-7 cells even at a high concentration of 1mg/mL whereas PTX-loaded HAI-NGs exhibited strong inhibition of MCF-7 cells. The in vivo pharmcokinetics, near-infrared imaging and biodistribution studies revealed that HAI-NGs significantly prolonged the blood circulation time and enhanced tumor accumulation of PTX. Interestingly, significantly enhanced CT imaging was observed for MCF-7 breast tumors in nude mice via either intratumoral or intravenous injection of HAI-NGs as compared to iodixanol. HAI-NGs fluoresence was distributed thoughout the whole tumor indicating deep tumor penetration. PTX-loaded HAI-NGs showed effective suppression of tumor growth with little systemic toxicity. HAI-NGs appear as a "smart" theranostic nanoplatform for the treatment of CD44 positive tumors.

Multidetector CT of pancreatic ductal adenocarcinoma: Effect of tube voltage and iodine load on tumour conspicuity and image quality.

OBJECTIVES: To compare a low-tube-voltage with or without high-iodine-load multidetector CT (MDCT) protocol with a normal-tube-voltage, normal-iodine-load (standard) protocol in patients with pancreatic ductal adenocarcinoma (PDAC) with respect to tumour conspicuity and image quality. METHODS: Thirty consecutive patients (mean age: 66 years, men/women: 14/16) preoperatively underwent triple-phase 64-channel MDCT examinations twice according to: (i) 120-kV standard protocol (PS; 0.75 g iodine (I)/kg body weight, n = 30) and (ii) 80-kV protocol A (PA; 0.75 g I/kg, n = 14) or protocol B (PB; 1 g I/kg, n = 16). Two independent readers evaluated tumour delineation and image quality blindly for all protocols. A third reader estimated the pancreas-to-tumour contrast-to-noise ratio (CNR). Statistical analysis was performed with the Chi-square test. RESULTS: Tumour delineation was significantly better in PB and PA compared with PS (P = 0.02). The evaluation of image quality was similar for the three protocols (all, P > 0.05). The highest CNR was observed with PB and was significantly better compared to PA (P = 0.02) and PS (P = 0.0002). CONCLUSION: In patients with PDAC, a low-tube-voltage, high-iodine-load protocol improves tumour delineation and CNR leading to higher tumour conspicuity compared to standard protocol MDCT. KEY POINTS: • Low-tube-voltage high-iodine-load MDCT improves pancreatic cancer conspicuity compared to a standard protocol. • The pancreas-to-tumour attenuation difference increases significantly by reducing the tube voltage. • The radiation exposure dose decreases by reducing the tube voltage.

Exponentially Decelerated Contrast Media Injection Rate Combined With a Novel Patient-Specific Contrast Formula Reduces Contrast Volume Administration and Radiation Dose During Computed Tomography Pulmonary Angiography.

CLINICAL RELEVANCE: Matching contrast injection timing with vessel dynamics significantly improves vessel opacification and reduces contrast dose in the assessment of pulmonary embolism during computed tomography (CT) pulmonary angiography. PURPOSE: The aim of this study was to investigate opacification of the pulmonary vasculature (PV) during CT pulmonary angiography using a patient-specific contrast formula (PSCF) and exponentially decelerated contrast media (EDCM) injection rate. MATERIALS AND METHODS: Institutional review board approved this retrospective study. Computed tomography pulmonary angiography was performed on 200 patients with suspected pulmonary embolism using a 64-channel CT scanner. Patient demographics were equally distributed. Patients were randomly assigned to 2 equal protocol groups: protocol A used a PSCF, and protocol B involved the use of a PSCF combined with EDCM. The mean cross-sectional opacification profile of 8 central and 11 peripheral PVs were measured for each patient, and arteriovenous contrast ratio was calculated. Protocols were compared using Mann-Whitney U nonparametric statistics. Jackknife alternative free-response receiver operating characteristic analyses were used to assess diagnostic efficacy. Interobserver variations were investigated using kappa methods. RESULTS: A number of pulmonary arteries demonstrated increases in opacification (P < 0.02) for protocol B compared with A, whereas opacification in all veins was reduced in protocol B (P < 0.03). Subsequently, increased arteriovenous contrast ratio in protocol B compared with A was observed at all anatomic locations (P < 0.0002). An increase in jackknife alternative free-response receiver operating characteristic figure of merit (P < 0.0002) and interobserver variation was observed with protocol B compared with protocol A (κ = 0.3-0.73). Mean contrast volume was reduced in protocol B (29 [4] mL) compared with protocol A (33 [9] mL). Mean effective radiation dose in protocol B (1.2 [0.4] mSv) was reduced by 14% compared with protocol A (1.4 [0.6] mSv). CONCLUSIONS: Significant improvements in visualization of the PV can be achieved with a low contrast volume using an EDCM and PSCF. The reduced risk of cancer induction is highlighted.

Ultrasmall superparamagnetic particles of iron oxide in patients with acute myocardial infarction: early clinical experience.

BACKGROUND: Inflammation following acute myocardial infarction (MI) has detrimental effects on reperfusion, myocardial remodelling, and ventricular function. Magnetic resonance imaging using ultrasmall superparamagnetic particles of iron oxide can detect cellular inflammation in tissues, and we therefore explored their role in acute MI in humans. METHODS AND RESULTS: Sixteen patients with acute ST-segment elevation MI were recruited to undergo 3 sequential magnetic resonance scans within 5 days of admission at baseline, 24 and 48 hours following no infusion (controls; n=6) or intravenous infusion of ultrasmall superparamagnetic particles of iron oxide (n=10; 4 mg/kg). T2*-weighted multigradient-echo sequences were acquired and R2* values were calculated for specific regions of interest. In the control group, R2* values remained constant in all tissues across all scans with excellent repeatability (bias of -0.208 s(-1), coefficient of repeatability of 26.96 s(-1); intraclass coefficient 0.989). Consistent with uptake by the reticuloendothelial system, R2* value increased in the liver (84±49.5 to 319±70.0 s(-1); P<0.001) but was unchanged in skeletal muscle (54±8.4 to 67.0±9.5 s(-1); P>0.05) 24 hours after administration of ultrasmall superparamagnetic particles of iron oxide. In the myocardial infarct, R2* value increased from 41.0±12.0 s(-1) (baseline) to 155±45.0 s(-1) (P<0.001) and 124±35.0 s(-1) (P<0.05) at 24 and 48 hours, respectively. A similar but lower magnitude response was seen in the remote myocardium, where it increased from 39±3.2 s(-1) (baseline) to 80±14.9 s(-1) (P<0.001) and 67.0±15.7 s(-1) (P<0.05) at 24 and 48 hours, respectively. CONCLUSIONS: Following acute MI, uptake of ultrasmall superparamagnetic particles of iron oxide occurs with the infarcted and remote myocardium. This technique holds major promise as a potential method for assessing cellular myocardial inflammation and left ventricular remodelling, which may have a range of applications in patients with MI and other inflammatory cardiac conditions.

Use of 18F-FDG PET/CT as a predictive biomarker of outcome in patients with head-and-neck non-squamous cell carcinoma.

OBJECTIVE: The purpose of this article is to establish whether pretreatment (18)F-FDG uptake predicts disease-free survival (DFS) and overall survival in patients with head-and-neck non-squamous cell carcinoma (SCC). MATERIALS AND METHODS: Eighteen patients (six women and 12 men; mean [± SD] age at diagnosis, 57.89 ± 13.54 years) with head-and-neck non-SCC were included. Tumor FDG uptake was measured by the maximum standardized uptake value (SUV(max)) and was corrected for background liver FDG uptake to derive the corrected SUV(max). Receiver operating characteristic analyses were used to predict the optimal corrected SUV(max) cutoffs for respective outcomes of DFS (i.e., absence of recurrence) and death. RESULTS: The mean corrected SUV(max) of the 18 head-and-neck tumors was 5.63 ± 3.94 (range, 1.14-14.29). The optimal corrected SUV(max) cutoff for predicting DFS and overall survival was 5.79. DFS and overall survival were significantly higher among patients with corrected SUV(max) < 6 than among patients with corrected SUV(max) ≥ 6. The mean DFS for patients with corrected SUV(max) < 6 was 25.7 ± 11.14 months, and the mean DFS for patients with corrected SUV(max) ≥ 6 was 7.88 ± 7.1 months (p < 0.018). Among patients with corrected SUV(max) < 6, none died, and the mean length of follow-up for this group was 35.2 ± 9.96 months. All of the patients who died had corrected SUV(max) ≥ 6, and the overall survival for this group was 13.28 ± 12.89 months (p < 0.001). CONCLUSION: FDG uptake, as measured by corrected SUV(max), may be a predictive imaging biomarker for DFS and overall survival in patients with head-and-neck non-SCC.

Squamous cell carcinoma of the palatine tonsils: FDG standardized uptake value ratio as a biomarker to differentiate tonsillar carcinoma from physiologic uptake.

PURPOSE: To quantify fluorine 18 ((18)F) fluorodeoxyglucose (FDG) uptake in the palatine tonsils to identify a sensitive and specific metric for distinguishing physiologic asymmetric uptake from squamous cell carcinoma (SCC). MATERIALS AND METHODS: This HIPAA-compliant retrospective study was approved by institutional review board. Informed consent requirements were waived. Twenty-six patients (seven female, 19 male; mean age, 53.46 years + or - 10.45 [standard deviation]) with tonsillar SCC were included. Twenty-six patients (seven female, 19 male; mean age, 61.77 years + or - 10.12) with head and neck carcinomas not involving the tonsils were included as control subjects. Tonsil standardized uptake values (SUVs) were measured bilaterally in each group. Independent-samples t test was used to compare mean SUVs, and Pearson correlation was used to evaluate association of FDG uptake between tonsils within control subjects. RESULTS: The mean maximum SUV (SUV(max)) of tonsil tumors was 9.36 + or - 4.54, which was significantly higher than that of contralateral cancer-free tonsils (2.54 + or - 0.88; P < .0001) and tonsils in control subjects (2.98 + or - 1.08; P < .0001). In patients with tonsillar cancer, the mean difference in SUV(max) between tonsils was 10.43 + or - 7.07, which was significantly greater than that in control subjects (0.62 + or - 0.54; P < .0001). The mean SUV(max) ratio between tonsils in patients with carcinoma was 3.79 + or - 1.69, which was threefold higher than in control subjects (1.18 + or - 0.13; P < .0001). For receiver operating characteristic analysis using SUV(max) ratio to differentiate benign uptake from SCC, the area under the curve was 1.00 (95% confidence interval: 1.00, 1.00). A cutoff ratio of 1.48 had 100% sensitivity and specificity. CONCLUSION: The SUV(max) ratio represents an accurate imaging biomarker for differentiating tonsillar SCC from physiologic (18)F-FDG uptake.

A method for reconstructing the arterial input function during helical CT: implications for myocardial perfusion distribution imaging.

PURPOSE: To determine if a multidetector computed tomographic (CT) image acquisition and analysis method can enable accurate measurement of the arterial input function (AIF) during first-pass adenosine stress helical multidetector CT angiography and to test the effect of using this method on the semiquantitative assessment of myocardial perfusion distribution. MATERIALS AND METHODS: The animal care and use committee of Johns Hopkins University approved the use of all procedures. The AIF was reconstructed by using a combination of bolus-tracking and time-registered helical multidetector CT data. After the AIF reconstruction method was validated in healthy animals, coronary stenosis was induced in seven dogs and contrast material-enhanced multidetector CT was performed during adenosine infusion (0.14-0.21 mg per kilogram of body weight per minute). Myocardial attenuation density (AD) parameters normalized to portions of the AIF were compared with microsphere myocardial blood flow (MBF) measurements at linear regression analysis. RESULTS: There was no significant difference between the area under the curve (AUC) for dynamic multidetector CT-derived AIF (3108 + or - 1250 [standard deviation]) and that for combined bolus-tracking and time-registered multidetector helical CT-derived AIF (3086 + or - 941) (P = .90). When AIF analysis was applied to helical multidetector CT myocardial perfusion measurements, the correlation between MBF and mean myocardial AD normalized to the AUC for the entire AIF was significant (R(2) = 0.82, P <.001). Myocardial AD normalized to the AUC for the AIF measured during helical multidetector CT correlated best with MBF (R(2) = 0.86, P <.001). CONCLUSION: The combination of bolus tracking and time-registered helical imaging enables reconstruction of the AIF during multidetector CT perfusion imaging. The helical CT AIF can be used to improve the semiquantitative assessment of myocardial perfusion distribution.

Computed tomography perfusion using first pass methods for lung nodule characterization.

OBJECTIVE: To evaluate computed tomography (CT) perfusion using first pass methods for lung nodule characterization. METHODS: Fifty-seven patients with 51 malignant and 6 benign nodules underwent first-pass, dynamic contrast-enhanced-CT (50 mL, 3-5 mL/s.). Kinetic analysis tools were CT Perfusion 3 (GEMS, Milwaukee, WI), a distributed parameter model approach, yielding blood volume (BV; mL/100 g), blood flow (BF; mL/min/100 g), mean transit time (1/s), and permeability surface area (mL/min/100 g), and an in-house Patlak-style analysis yielding fractional BV (mL/100 g) and an estimate of extraction (Kps, mL/100 g/min). RESULTS: CT Perfusion 3 parameters in malignant and benign nodules were: mean transit time 10.1 +/- 0.9 1/s versus 11.1 +/- 3.1 1/s (ns), permeability surface 23.3 +/- 9.1 mL/min/100 g versus 19.6 +/- 10.3 mL/min/100 g (ns), BF 111.3 +/- 8.7 mL/min/100 g versus 39.1+/- 5.7 mL/min/100 g (P < 0.001), BV 9.3+/- 0.7 mL/100 g versus 4.1 +/- 1.1 mL/100 g (P < 0.002); Patlak parameters were: Kps 13.3 +/- 1.2 mL/100 g/min versus 3.9 +/- 0.8 mL/100 g/min (P < 0.001), BV 8.4 +/- 0.8 mL/100 g versus 3.6 +/- 1.3 mL/100 g (P < 0.01). The two kinetic methods show good agreement for BV estimation (Bland-Altman plot). The limits of agreement (bias +/-2 standard deviation of bias) were 1.2 +/- 5.3 mL/100 g. CONCLUSION: CT Perfusion using first pass modeling appears feasible for lung nodule characterization. Given the short acquisition duration used, weaknesses of the modeling methods are exposed. Nonetheless, microvascular characterization in terms of BF, BV, or Kps appears useful in distinguishing malignant from benign nodules.

Quadruple-phase MDCT of the liver in patients with suspected hepatocellular carcinoma: effect of contrast material flow rate.

OBJECTIVE: The purposes of this study were to evaluate the effect of contrast material flow rate (3 mL/sec vs 5 mL/sec) on the detection and visualization of hepatocellular carcinoma (HCC) with MDCT and the safety profile of iodixanol at different injection rates. SUBJECTS AND METHODS: In a prospective, randomized multicenter trial, 97 patients (83 men and 14 women, with a mean age of 64 years) suspected of having HCC underwent quadruple-phase (double arterial, portal venous, delayed phase) 4-16-MDCT. Patients were randomized to receive iodixanol, 320 mg I/mL (1.5 mL/kg body weight), at a flow rate of 3 mL/sec (48 patients) or 5 mL/sec (49 patients). Qualitative (lesion detection, image quality) and quantitative (liver and aortic enhancement, tumor-liver contrast) analyses and safety assessment were performed. RESULTS: Overall, 145 HCCs were detected in the 5 mL/sec group and 100 HCCs in the 3 mL/sec group (p < 0.05). More lesions equal to or less than 1 cm were detected at 5 mL/sec (33 vs 16 lesions). The late arterial phase showed significantly more lesions than the early, arterial phase (133 vs 100 and 96 vs 67 lesions, respectively, p < 0.0001). Hyperattenuating HCCs were better visualized in the late arterial phase at 5 mL/sec (excellent visualization: 54% vs 27%). Using a flow of 5 mL/sec did not increase the rate of patient discomfort or contrast media-related adverse events. Most discomfort in both groups was of mild intensity and there was no severe discomfort. CONCLUSION: For detection of HCC with MDCT, a higher flow rate of 5 mL/sec is recommended. Visualization of hyperattenuating HCC is improved with no greater discomfort or adverse events.

Voxel-based mouse and rat models for internal dose calculations.

UNLABELLED: The ability to estimate absorbed doses in experimental animals to which radiolabeled material has been administered may be important in explaining and controlling potential radiation toxicity observed during preclinical trials. Most previously reported models for establishing doses to small animals have been stylized and mathematically based. This study establishes dose factors for internal sources in realistic models of a typical mouse and a typical rat, based on image data obtained using a dedicated small-animal CT scanner. METHODS: A transgenic mouse (body mass, 27 g) and a Sprague-Dawley rat (body mass, 248 g) were imaged using the dedicated small-animal CT scanner. Identified organs were segmented using computer tools that Vanderbilt University applies to process human images for 3-dimensional dosimetry. Monte Carlo N-particle transport code (MCNP) input files were prepared from the 3-dimensional, voxel-based image data. Using methods established for human studies, radiation transport calculations of absorbed fractions (AFs) were performed using MCNP, version 4C, on the segmented images, and dose conversion factors for several radionuclides were developed. RESULTS: AFs were established at discrete energies for electron and photon sources assumed to be uniformly distributed throughout approximately 10 source and target regions in both models. Electron self-irradiation AFs were significantly less than 1.0 for many organs, at energies above 0.5 MeV, and significant cross irradiation was observed for high-energy electrons, such as those from (90)Y or (188)Re, in many organs. Calculated dose conversion factors reflected these trends and agreed well with the results of other authors who have undertaken similar investigations. CONCLUSION: The AFs calculated in this study will be useful in determining the dose to organs for mice and rats similar in size to those studied here. The segmented, voxel-based models developed here can be used for external dose calculations as well.

Quantifying the effect of IV contrast media on integrated PET/CT: clinical evaluation.

OBJECTIVES: The use of IV contrast media in PET/CT can result in an overestimation of PET attenuation factors that potentially can affect interpretation. The objective of this study was to quantify the effect of IV contrast media in PET/CT and assess its impact on patients with intrathoracic malignancies. MATERIALS AND METHODS: Nine patients had CTs performed with and without IV contrast media followed by (18)F-FDG PET. PET images were reconstructed using contrast-enhanced and unenhanced CT. To quantify the effect of contrast media on standardized uptake values (SUV), similar regions of interest (ROIs) were drawn on the subclavian vein, heart, liver, spleen, and site of malignancy on both CT and corresponding reconstructed PET images, and the mean and maximum values were compared. In addition, two physicians blinded to the imaging parameters that were used evaluated the reconstructed PET images to assess whether IV contrast media had an effect on clinical interpretation. RESULTS: For all patient studies, the subclavian vein region on the ipsilateral side of contrast media administration had the highest increase in CT numbers with a corresponding average SUV(max) increase of 27.1%. Similarly, ROIs of the heart and at the site of malignancy showed an increase in the maximum attenuation value with a corresponding average SUV(max) increase of 16.7% and 8.4%, respectively. Other locations had relatively small attenuation value differences with a correspondingly negligible SUV variation. CONCLUSION: Although there is a significant increase in SUV in regions of high-contrast concentration when contrast-enhanced CT is used for attenuation correction, this increase is clinically insignificant. Accordingly, in PET/CT, IV contrast-enhanced CT can be used in combination with the PET to evaluate patients with cancer.

Intestinal permeability of x-ray constrast media iodixanol and iohexol during bacterial overgrowth of small intestines in rats.

To investigate the recovery of iodinated water-soluble contrast medium from small bowel with small morphological alterations, iohexol or iodixanol was instilled through an orogastric tube in rats 14 days after surgery that established a self-filling blind loop in the jejunum. This rat model induced small bowel bacterial overgrowth with only minor abnormalities observed on histology and scanning electron microscopy. Animals with end-to-end anastomosis of the jejunum or unoperated rats served as controls. Compared with unoperated animals, urinary recovery of iohexol and iodixanol was significantly higher in both groups that underwent surgery. Moreover, the contrast medium recovery was numerically higher in the self-filling blind loop group given iodixanol than in the end-to-end anastomosis group, although not statistically significant, P = 0.09. Our results indicate that iohexol and iodixanol may detect small barrier impairments in the intestines. Iodixanol, the largest of the two, may seem to differentiate better between normal and minimally impaired intestinal barrier.

Safety and pharmacokinetics of iotrolan in hysterosalpingography. Retention and irritability compared with Lipiodol.

RATIONALE AND OBJECTIVES: The authors compared the safety and pharmacokinetics of Iotrolan (water-soluble) in hysterosalpingography (HSG) with those of Lipiodol (oil-soluble). METHODS: Iotrolan and Lipiodol were administered intraperitoneally at doses of 100 mg iodine/kg to female rabbits. Retention in the body was investigated by x-ray imaging, plasma kinetics, and urinary and fecal excretion. Irritability in the abdomen was investigated by histologic examination. RESULTS: Iotrolan was entirely excreted into the urine within 2 days after administration. Conversely, Lipiodol was excreted into the urine, had a half-life of 50 days, and was retained for more than 21 days in the abdomen. Iotrolan induced no inflammatory reaction in the abdomen, whereas Lipiodol induced a marked abdominal inflammatory reaction, including granuloma formation. Iotrolan had no effect on iodine concentration in the thyroid; Lipiodol increased iodine concentration significantly. CONCLUSIONS: Iotrolan, which is a water-soluble and nonionic dimeric contrast medium, has potential greater safety for use in HSG than Lipiodol.