Hypoxia-Targeting Fluorescent Nanobodies for Optical Molecular Imaging of Pre-Invasive Breast Cancer

Purpose

The aim of this work was to develop a CAIX-specific nanobody conjugated to IRDye800CW for molecular imaging of pre-invasive breast cancer.

Procedures

CAIX-specific nanobodies were selected using a modified phage display technology, conjugated site-specifically to IRDye800CW and evaluated in a xenograft breast cancer mouse model using ductal carcinoma in situ cells (DCIS).

Results

Specific anti-CAIX nanobodies were obtained. Administration of a CAIX-specific nanobody into mice with DCIS xenografts overexpressing CAIX showed after 2 h a mean tumor-to-normal tissue ratio (TNR) of 4.3?±?0.6, compared to a TNR of 1.4?±?0.2 in mice injected with the negative control nanobody R2-IR. In DCIS mice, a TNR of 1.8?±?0.1 was obtained. Biodistribution studies demonstrated an uptake of 14.0?±?1.1 %I.D./g in DCIS?+?CAIX tumors, 4.6?±?0.8 %I.D./g in DCIS tumors, while 2.0?±?0.2 %I.D./g was obtained with R2-IR.

Conclusions

These results demonstrate the successful generation of a CAIX-specific nanobody-IRDye800CW conjugate that can be used for rapid imaging of (pre-)invasive breast cancer.

     

700-nm Zwitterionic Near-Infrared Fluorophores for Dual-Channel Image-Guided Surgery

Purpose

The purpose of this study was to develop a family of 700-nm zwitterionic pentamethine indocyanine near-infrared fluorophores that would permit dual-channel image-guided surgery.

Procedures

Three complementary synthetic schemes were used to produce novel zwitterionic chemical structures. Physicochemical, optical, biodistribution, and clearance properties were compared to Cy5.5, a conventional pentamethine indocyanine now used for biomedical imaging.

Results

ZW700-1a, ZW700-1b, and ZW700-1c were synthesized, purified, and analyzed extensively in vitro and in vivo. All molecules had extinction coefficients ≥199,000 M^?1 cm^?1, emission ≥660 nm, and stability ≥99 % after 24 h in warm serum. In mice, rats, and pigs, ≥80 % of the injected dose was completely eliminated from the body via renal clearance within 4 h. Either alone or conjugated to a tumor targeting ligand, ZW700-1a permitted dual-channel, high SBR, and simultaneous imaging with 800-nm NIR fluorophores using the FLARE® imaging system.

Conclusions

Novel 700-nm zwitterionic NIR fluorophores enable dual-NIR image-guided surgery.

     

Fusion imaging with contrast-enhanced ultrasonography for evaluating the early therapeutic efficacy of radiofrequency ablation for small hypervascular hepatocellular carcinomas with iso-echoic or unclear margins on conventional ultrasonography

Purpose

We evaluated the efficacy of fusion imaging combining contrast-enhanced ultrasonography (CEUS) images and arterial phase contrast-enhanced CT (CECT) or hepatobiliary phase magnetic resonance imaging with gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (EOB-MRI) images for the early evaluation of the effectiveness of radiofrequency ablation (RFA) for small hypervascular hepatocellular carcinoma (HCC) with iso-echoic or unclear margins on conventional US.

Methods

Forty HCCs (22 iso-echoic and 18 unclear margin lesions) with mean diameters of 13.7 mm were treated using RFA under the guidance of fusion imaging with CEUS. The adequacy of RFA was evaluated using fusion imaging with CEUS 1 day after RFA. CECT or EOB-MRI was performed 1 month after RFA. We reviewed the images obtained using both modalities.

Results

When the 1-month CECT or EOB-MRI scans were used as the reference standard, the sensitivity, specificity, and accuracy of the 1-day fusion imaging for the diagnosis of the adequate ablation of these HCCs were 97, 100, and 98%, respectively; the kappa value for the agreement between the findings using the two modalities was 0.655.

Conclusion

Fusion imaging with CEUS appears to be a useful method for the early evaluation of the efficacy of RFA for the treatment of HCCs with iso-echoic or unclear margins on conventional US.

     

In Vivo HER2-Targeted Magnetic Resonance Tumor Imaging Using Iron Oxide Nanoparticles Conjugated with Anti-HER2 Fragment Antibody

Purpose

The feasibility of iron oxide nanoparticles (IONPs) conjugated with anti-epidermal growth factor receptor 2 (HER2) single-chain antibody (scFv-IONPs) as novel HER2-targeted magnetic resonance (MR) contrast agents was investigated.

Procedures

The scFv-IONPs were prepared and identified. For in vitro MRI, NCI-N87 (HER2 high expression) and SUIT2 (low expression) cells were incubated with scFv-IONPs. For in vivo MRI, NCI-N87 and SUIT2 tumor-bearing mice were intravenously injected with scFv-IONPs and imaged before and 24 h post-injection.

Results

The scFv-IONPs demonstrated high transverse relaxivity (296.3 s^?1 mM^?1) and affinity toward HER2 (K_D?=?11.7 nM). In the in vitro MRI, NCI-N87 cells treated with scFv-IONPs exhibited significant MR signal reduction (44.6 %) than SUIT2 cells (6.8 %). In the in vivo MRI, decrease of MR signals in NCI-N87 tumors (19.3 %) was more notable than that in SUIT2 tumors (6.2 %).

Conclusions

The scFv-IONPs enabled HER2-specific tumor MR imaging, suggesting the potential of scFv-IONPs as a robust HER2-targeted MR contrast agent.

     

Microwave ablation of liver tumors: degree of tissue contraction as compared to RF ablation

Purpose

To compare the amount of tissue contraction after microwave (MW) versus radiofrequency (RF) ablation of liver tumors.

Materials and methods

Seventy-five hepatic tumors in 65 patients who underwent percutaneous MW or RF ablations were included in this retrospective study. All patients underwent MRI within 6 months before the ablation and 24 h after the procedure. Two blinded radiologists, by consensus, performed measurements on the corresponding series of pre and post-ablation MRI. Absolute and relative contraction of liver, tumor, and control were calculated and compared.

Results

Thirty-one patients underwent MW ablations, and 44 patients underwent RF ablations. The absolute and relative contraction of the ablation zone were significantly greater with MW than RF ablation (p = 0.003 to <0.001). Thirty-two lesions were visible on both pre- and post-ablation MRI. MW ablation had significantly more tumor contraction as compared to RF ablation (p = 0.003 to 0.009). The control measurements demonstrated no significant difference in normal tissue variation between MW and RF groups.

Conclusions

MW ablation of hepatic tumors produced significantly more contraction of tumor and ablated hepatic tissue compared to RF ablation. Tissue contraction should be taken into account during pre-procedural planning and assessing treatment response by comparing pre- and post-ablation images.

     

A Real-Time Non-invasive Auto-bioluminescent Urinary Bladder Cancer Xenograft Model

Purpose

The study was to develop an auto-bioluminescent urinary bladder cancer (UBC) xenograft animal model for pre-clinical research.

Procedure

The study used a humanized, bacteria-originated lux reporter system consisting of six (luxCDABEfrp) genes to express components required for producing bioluminescent signals in human UBC J82, J82-Ras, and SW780 cells without exogenous substrates. Immune-deficient nude mice were inoculated with Lux-expressing UBC cells to develop auto-bioluminescent xenograft tumors that were monitored by imaging and physical examination.

Results

Lux-expressing auto-bioluminescent J82-Lux, J82-Ras-Lux, and SW780-Lux cell lines were established. Xenograft tumors derived from tumorigenic Lux-expressing auto-bioluminescent J82-Ras-Lux cells allowed a serial, non-invasive, real-time monitoring by imaging of tumor development prior to the presence of palpable tumors in animals.

Conclusions

Using Lux-expressing auto-bioluminescent tumorigenic cells enabled us to monitor the entire course of xenograft tumor development through tumor cell implantation, adaptation, and growth to visible/palpable tumors in animals.

     

Applying Amide Proton Transfer MR Imaging to Hybrid Brain PET/MR: Concordance with Gadolinium Enhancement and Added Value to [<Superscript>18</Superscript>F]FDG PET

Purpose

The purpose of this study is to evaluate the diagnostic concordance and metric correlations of amide proton transfer (APT) imaging with gadolinium-enhanced magnetic resonance imaging (MRI) and 2-deoxy-2-[¹⁸F-]fluoro-D-glucose ([¹⁸F]FDG) positron emission tomography (PET), using hybrid brain PET/MRI.

Procedures

Twenty-one subjects underwent brain gadolinium-enhanced [¹⁸F]FDG PET/MRI prospectively. Imaging accuracy was compared between unenhanced MRI, MRI with enhancement, APT-weighted (APTW) images, and PET based on six diagnostic criteria. Among tumors, the McNemar test was further used for concordance assessment between gadolinium-enhanced imaging, APT imaging, and [¹⁸F]FDG PET. As well, the relation of metrics between APT imaging and PET was analyzed by the Pearson correlation analysis.

Results

APT imaging and gadolinium-enhanced MRI showed superior and similar diagnostic accuracy. APTW signal intensity and gadolinium enhancement were concordant in 19 tumors (100 %), while high [¹⁸F]FDG avidity was shown in only 12 (63.2 %). For the metrics from APT imaging and PET, there was significant correlation for 13 hypermetabolic tumors (P < 0.05) and no correlation for the remaining six [¹⁸F]FDG-avid tumors.

Conclusions

APT imaging can be used to increase diagnostic accuracy with no need to administer gadolinium chelates. APT imaging may provide an added value to [¹⁸F]FDG PET in the evaluation of tumor metabolic activity during brain PET/MR studies.

     

Comparison of tumor vascularity and hemodynamics in three rat hepatoma models

Purpose

To compare tumor vascularity and hemodynamics in three rat hepatoma models: N1-S1 cells in Sprague–Dawley rats, McA-RH7777 cells in Sprague–Dawley rats, and 13762 MAT B III cells in F344 rats.

Methods

The three rat hepatoma models were induced in five rats per group. After confirming that the tumors grew up to 10 mm on magnetic resonance imaging, the rats underwent dynamic contrast-enhanced ultrasonography (DCE-US). Afterward, the rats were euthanized for histologic analyses. The Kruskal–Wallis test was used to compare the rat hepatoma models. Correlation coefficients were calculated between the microvessel density (MVD) and DCE-US parameters.

Results

On DCE-US imaging, arterial enhancement and washout were demonstrated in all N1-S1 tumors, while persistent peripheral enhancement on arterial to portal phases was shown in all 13762 MAT B III tumors. The McA-RH7777 tumors presented diverse enhancement patterns on arterial and portal phases. There were no significant differences in DCE-US parameters among the three hepatoma groups, while MVD was correlated with peak intensity (r = 0.565, p = 0.044), mean transit time (r = ?0.559, p = 0.047), and time to peak (r = ? 0.617, p = 0.025) of individual rats. The necrosis ratio was significantly different between the models (p = 0.031); 13762 MAT B III showed a significantly higher necrosis ratio than N1-S1 (p < 0.050 by post hoc test).

Conclusion

The N1-S1 tumor may be suitable as a model to investigate hypervascular hepatic tumors of the liver in DCE-US such as hepatocellular carcinoma among the three tumors.

     

A Randomized,Clinical Trial to Evaluate Efficacy and Tolerability of Trypsin:Chymotrypsin as Compared to Serratiopeptidase and Trypsin:Bromelain:Rutoside in Wound Management

Introduction

Systemic enzyme therapy can play an important role in maintaining normal inflammatory processes within the body and thereby helps support and speed up healing. In the course of the anti-inflammatory action, enzymes degrade damaged cells and necrotic material and, through the inactivation of mediators and toxic products, they restrict the edema and pain.

Method

The study conducted at Grant Medical College, Mumbai, India was a clinical trial comparing the efficacy and tolerability of three oral enzyme treatment groups—oral tablets containing trypsin:chymotrypsin (TC) (Chymoral Forte^®), serratiopeptidase (S) 5 mg oral tablets, and oral enzyme tablets containing trypsin 48 mg, bromelain 90 mg, and rutoside 100 mg (TBR)—to evaluate their healing potential in surgical wounds after orthopedic surgery.

Results

A total of 75 patients were screened, randomized, and divided into three groups in 1:1:1 ratio receiving either of the three treatments. In the TC group, erythema was significantly reduced from 3.44 on day 3 to 1.16 on day 10 (p < 0.01). There was significantly better reduction in erythema scores in the TC group as compared to S and TBR groups (p < 0.05) at each follow-up visit. Similarly reduction in the local irritation, wound discharge, edema, induration, and tenderness score with TC treatment at the end of the study was significantly higher than that observed in the other two groups. In addition TC showed significant reduction in pain on the VAS scale (p < 0.01). Global assessment of response to therapy for efficacy and tolerability was reported to be good to excellent in 88% and 92% of the patients on TC as compared to 12% and 8% with S and 12% and 8% with TBR.

Conclusion

TC provides a better resolution of symptoms of inflammation after orthopedic surgery as compared to S and TBR, thus facilitating better wound healing. Further studies are warranted to confirm the findings.

Trial Registration

Clinical Trial Registry of India (Reg. No. CTRI/2011/07/001920).

     

Non-invasive PET Imaging of PARP1 Expression in Glioblastoma Models

Purpose

The current study presents [¹⁸F]PARPi as imaging agent for PARP1 expression.

Procedures

[¹⁸F]PARPi was generated by conjugating a 2H-phthalazin-1-one scaffold to 4-[¹⁸F]fluorobenzoic acid. Biochemical assays, optical in vivo competition, biodistribution analysis, positron emission tomography (PET)/X-ray computed tomography, and PET/magnetic resonance imaging studies were performed in subcutaneous and orthotopic mouse models of glioblastoma.

Results

[¹⁸F]PARPi shows suitable pharmacokinetic properties for brain tumor imaging (IC₅₀?=?2.8?±?1.1 nM; logP_CHI?=?2.15?±?0.41; plasma-free fraction?=?63.9?±?12.6 %) and accumulates selectively in orthotopic brain tumor tissue. Tracer accumulation in subcutaneous brain tumors was 1.82?±?0.21 %ID/g, whereas in healthy brain, the uptake was only 0.04?±?0.01 %ID/g.

Conclusions

[¹⁸F]PARPi is a selective PARP1 imaging agent that can be used to visualize glioblastoma in xenograft and orthotopic mouse models with high precision and good signal/noise ratios. It offers new opportunities to non-invasively image tumor growth and monitor interventions.

     

Translocator Protein PET Imaging in a Preclinical Prostate Cancer Model

Purpose

The identification and targeting of biomarkers specific to prostate cancer (PCa) could improve its detection. Given the high expression of translocator protein (TSPO) in PCa, we investigated the use of [¹⁸F]VUIIS1008 (a novel TSPO-targeting radioligand) coupled with positron emission tomography (PET) to identify PCa in mice and to characterize their TSPO uptake.

Procedures

Pten^pc?/?, Trp53^pc?/? prostate cancer-bearing mice (n = 9, 4–6 months old) were imaged in a 7T MRI scanner for lesion localization. Within 24 h, the mice were imaged using a microPET scanner for 60 min in dynamic mode following a retro-orbital injection of ~ 18 MBq [¹⁸F]VUIIS1008. Following imaging, tumors were harvested and stained with a TSPO antibody. Regions of interest (ROIs) were drawn around the tumor and muscle (hind limb) in the PET images. Time-activity curves (TACs) were recorded over the duration of the scan for each ROI. The mean activity concentrations between 40 and 60 min post radiotracer administration between tumor and muscle were compared.

Results

Tumor presence was confirmed by visual inspection of the MR images. The uptake of [¹⁸F]VUIIS1008 in the tumors was significantly higher (p < 0.05) than that in the muscle, where the percent injected dose per unit volume for tumor was 7.1 ± 1.6 % ID/ml and that of muscle was < 1 % ID/ml. In addition, positive TSPO expression was observed in tumor tissue analysis.

Conclusions

The foregoing preliminary data suggest that TSPO may be a useful biomarker of PCa. Therefore, using TSPO-targeting PET ligands, such as [¹⁸F]VUIIS1008, may improve PCa detectability and characterization.

     

A Novel Unsupervised Segmentation Approach Quantifies Tumor Tissue Populations Using Multiparametric MRI: First Results with Histological Validation

Purpose

We aimed to precisely estimate intra-tumoral heterogeneity using spatially regularized spectral clustering (SRSC) on multiparametric MRI data and compare the efficacy of SRSC with the previously reported segmentation techniques in MRI studies.

Procedures

Six NMRI nu/nu mice bearing subcutaneous human glioblastoma U87 MG tumors were scanned using a dedicated small animal 7T magnetic resonance imaging (MRI) scanner. The data consisted of T2 weighted images, apparent diffusion coefficient maps, and pre- and post-contrast T2 and T2* maps. Following each scan, the tumors were excised into 2–3-mm thin slices parallel to the axial field of view and processed for histological staining. The MRI data were segmented using SRSC, K-means, fuzzy C-means, and Gaussian mixture modeling to estimate the fractional population of necrotic, peri-necrotic, and viable regions and validated with the fractional population obtained from histology.

Results

While the aforementioned methods overestimated peri-necrotic and underestimated viable fractions, SRSC accurately predicted the fractional population of all three tumor tissue types and exhibited strong correlations (r_necrotic = 0.92, r_{peri-necrotic} = 0.82 and r_viable = 0.98) with the histology.

Conclusions

The precise identification of necrotic, peri-necrotic and viable areas using SRSC may greatly assist in cancer treatment planning and add a new dimension to MRI-guided tumor biopsy procedures.

     

Characterization of “γ-Eye”: a Low-Cost Benchtop Mouse-Sized Gamma Camera for Dynamic and Static Imaging Studies

Purpose

Several preclinical imaging systems are commercially available, but their purchase and maintenance costs make them unaffordable for the majority of small- and medium-sized groups. Taking into account the needs of average users, we developed “γ-eye”, a mouse-sized, benchtop γ-camera suitable for in vivo scintigraphic imaging.

Procedures

The γ-eye is based on two position-sensitive photomultiplier tubes, coupled to a CsI(Na) pixelated scintillator and a low-energy lead collimator with parallel hexagonal holes.

Results

The spatial resolution of the system is 2 mm at 0 mm. The energy resolution is 26 % at 140 keV and the maximum recorded sensitivity 210 cps/MBq. The system was evaluated in a proof-of-concept animal study, using three different clinical Tc-99m-labeled radiopharmaceuticals. Phantom and animal studies demonstrate its ability to provide semiquantitative results even for short scans.

Conclusions

Systems’ performance, dimensions, and cost make γ-eye a unique solution for efficient whole-body mouse nuclear imaging.

     

Creatine CEST MRI for Differentiating Gliomas with Different Degrees of Aggressiveness

Purpose

Creatine (Cr) is a major metabolite in the bioenergetic system. Measurement of Cr using conventional MR spectroscopy (MRS) suffers from low spatial resolution and relatively long acquisition times. Creatine chemical exchange saturation transfer (CrCEST) magnetic resonance imaging (MRI) is an emerging molecular imaging method for tissue Cr measurements. Our previous study showed that the CrCEST contrast, obtained through multicomponent Z-spectral fitting, was lower in tumors compared to normal brain, which further reduced with tumor progression. The current study was aimed to investigate if CrCEST MRI can also be useful for differentiating gliomas with different degrees of aggressiveness.

Procedures

Intracranial 9L gliosarcoma and F98 glioma bearing rats with matched tumor size were scanned with a 9.4 T MRI scanner at two time points. CEST Z-spectra were collected using a customized sequence with a frequency-selective rectangular saturation pulse (B₁?=?50 Hz, duration?=?3 s) followed by a single-shot readout. Z spectral data were fitted pixel-wise with five Lorentzian functions, and maps of CrCEST peak amplitude, linewidth, and integral were produced. For comparison, single-voxel proton MR spectroscopy (¹H-MRS) was performed to quantify and compare the total Cr concentration in the tumor.

Results

CrCEST contrasts decreased with tumor progression from weeks 3 to 4 in both 9L and F98 phenotypes. More importantly, F98 tumors had significantly lower CrCEST integral compared to 9L tumors. On the other hand, integrals of other Z-spectral components were unable to differentiate both tumor progression and phenotype with limited sample size.

Conclusions

Given that F98 is a more aggressive tumor than 9L, this study suggests that CrCEST MRI may help differentiate gliomas with different aggressiveness.

     

Multimodality imaging to assess immediate response following irreversible electroporation in patients with malignant hepatic tumors

Purpose

To assess the diagnostic accuracy of contrast-enhanced ultrasound (CEUS), contrast-enhanced multiphase CT (CECT), and gadoxetic acid-enhanced MRI (EOB-MRI) in identifying residual tumor in the subacute follow-up of patients with malignant hepatic tumors treated by irreversible electroporation (IRE).

Methods

We enrolled 16 patients with 21 hepatic lesions treated by IRE and examined by CEUS and CECT at 1 day after IRE and by EOB-MRI at 7 days after IRE. Follow-up examinations by EOB-MRI or CECT and CEUS were performed at 3-month intervals. Two radiologists independently reviewed the images and assessed the probability of residual tumor using a five-point scale with receiver operating characteristic (ROC) curve analysis. The sensitivity and specificity were also evaluated. Verifiable local recurrence was assessed using follow-up imaging as the reference standard.

Results

The mean area under the ROC curve was significantly higher for CEUS (0.980) than for CECT (0.742, P < 0.01) and EOB-MRI (0.806, P < 0.01), as were the sensitivity and specificity (mean 85.7 and 85.7% for CEUS, respectively, vs 64.3 and 46.4% for CECT and 78.6 and 64.3% for EOB-MRI).

Conclusion

CEUS was found to be superior to CECT and EOB-MRI for the diagnosis of residual tumor in the subacute phase following IRE.

     

Can diffusion-weighted magnetic resonance imaging predict tumor recurrence of uterine cervical cancer after concurrent chemoradiotherapy?

Purpose

To retrospectively investigate the utility of diffusion-weighted imaging (DWI) for predicting clinical outcome after concurrent chemoradiotherapy (CCRT) in uterine cervical cancer.

Materials and methods

Seventy-four consecutive patients with biopsy-proven cervical cancer who received CCRT underwent DWI at 3T. All patients had MR examinations before therapy (preTx) and at 4 weeks of initiating therapy (midTx). At each point, ADC (apparent diffusion coefficient) was measured in the tumors and ADC change between preTx and midTx were also calculated. For predicting tumor recurrence, MR variables and clinical variables were evaluated and the results were compared.

Results

During a mean follow-up of 32.1 months, tumor recurrence developed in 15 (20%) patients: local recurrence (n = 7), distant metastasis (n = 5), and both (n = 3). MidTx tumor ADCs and tumor ADC changes between preTx and midTx were significantly different between the recurrence and non-recurrence groups (P < 0.05), while preTx tumor ADCs were not significantly different between the groups (P = 0.892). Univariate analysis revealed that histologic type, stage, preTx tumor size and volume, and tumor ADC change were significantly related to tumor recurrence (all P < 0.05). However, on multivariate analysis, tumor ADC changes [hazard ratio (HR) 0.886; 95% confidence interval (CI) 0.836–0.940; P = 0.001] and histological type (HR 6.063; 95% CI 1.404–26.187; P = 0.016) were the significant independent predictors of tumor recurrence.

Conclusion

Tumor ADC changes between preTx and midTx might be a useful biomarker for the prediction of cervical cancer recurrence after CCRT.

     

Comparative Study of Tumor Targeting and Biodistribution of pH (Low) Insertion Peptides (pHLIP<Superscript>®</Superscript> Peptides) Conjugated with Different Fluorescent Dyes

Purpose

Acidification of extracellular space promotes tumor development, progression, and invasiveness. pH (low) insertion peptides (pHLIP^® peptides) belong to the class of pH-sensitive membrane peptides, which target acidic tumors and deliver imaging and/or therapeutic agents to cancer cells within tumors.

Procedures

Ex vivo fluorescent imaging of tissue and organs collected at various time points after administration of different pHLIP^® variants conjugated with fluorescent dyes of various polarity was performed. Methods of multivariate statistical analyses were employed to establish classification between fluorescently labeled pHLIP^® variants in multidimensional space of spectral parameters.

Results

The fluorescently labeled pHLIP^® variants were classified based on their biodistribution profile and ability of targeting of primary tumors. Also, submillimeter-sized metastatic lesions in lungs were identified by ex vivo imaging after intravenous administration of fluorescent pHLIP^® peptide.

Conclusions

Different cargo molecules conjugated with pHLIP^® peptides can alter biodistribution and tumor targeting. The obtained knowledge is essential for the design of novel pHLIP^®-based diagnostic and therapeutic agents targeting primary tumors and metastatic lesions.

     

CT imaging of early local recurrence of pancreatic adenocarcinoma following pancreaticoduodenectomy

Purpose

The objectives of this retrospective study were to describe the characteristics and topography of pancreatic ductal adenocarcinoma and its early local recurrence after pancreaticoduodenectomy and identify predictive factors of local early recurrence by imaging computed tomography (CT).

Methods

The institutional review board approved the study and did require additional informed consent for reviewing the patients’ medical records and images. Patients who underwent pancreaticoduodenectomy for ductal adenocarcinoma, a preoperative CT scan, and adequate postoperative CT were included. After postoperative imaging, correlations among clinical and histological characteristics and preoperative imaging were evaluated.

Results

Among the 123 patients who underwent pancreaticoduodenectomy, 48 patients had sufficient follow-up imaging and were included in this study. A total of 33 patients experienced local early recurrence (Group 1), and 15 exhibited no local recurrence (Group 2). Local recurrence consisted of two types of anomalies: tissue nodules on surgical clips (94 %) and peri-arterial encasement (82 %). On preoperative imaging, the tumor diameter (p = 0.02) and the presence of a venous borderline resectable tumor (p < 0.0001) were predictive of local recurrence.

Conclusions

Tissue nodules on surgical clips and arterial encasement characterize early local recurrence, and nodules and encasement should not be considered common post-operative infiltration. The role of the radiologist is essential to assess the predictive factors of recurrence and to identify early local recurrence.

     

Fundamentals of Cardiovascular Molecular Imaging: a Review of Concepts and Strategies

Purpose of the Review

In this review, we will discuss the basic fundamentals of how to perform molecular imaging to better understand the underlying mechanisms contributing to cardiovascular disease.

Report Findings

Molecular imaging combines molecular biology with in vivo imaging. Molecular probes are used to target discrete biological processes such as cell death, inflammation, and angiogenesis. These probes emit signals that are detected by traditional imaging systems. Because the same disease processes can manifest in individuals in different ways, molecular imaging may emerge as an important strategy for delivering precision medicine.

Summary

Molecular imaging is a powerful tool that may help physicians provide more personalized care in the near future.

     

Small (&lt;4 cm) clear cell renal cell carcinoma: correlation between CT findings and histologic grade

Purpose

To evaluate the correlation between CT findings and histologic grade of small clear cell renal cell carcinoma (ccRCC).

Methods

CT scans of 101 patients with small ccRCC were reviewed independently by two radiologists for tumor size, shape, margin, encapsulation, enhancement pattern, and visual relative enhancement. Enhancement patterns were defined according to the percentage of uniform enhancement [pattern 1, homogeneous (≥90%); pattern 2, relatively homogeneous (≥75 and <90%); and pattern 3, heterogeneous (<75%)]. Quantitative parameters representing attenuation and degree of enhancement were calculated. Histologic grade was classified as low (Fuhrman grade I or II) and high (Fuhrman grade III or IV). CT imaging variables were analyzed using univariate and multivariate analyses.

Results

A total of 63 low-grade and 38 high-grade small ccRCCs were assessed. Low-grade tumors differed from high-grade tumors with respect to enhancement pattern 1 or 2 (p < 0.001 and p < 0.001), smaller size (p = 0.002 and p = 0.001), and lower attenuation on unenhanced scan (p < 0.001 and p = 0.008). In multivariate analysis, enhancement pattern 1 or 2 and low attenuation (≤30 HU) were identified as independent predictors of low-grade ccRCC. Accuracy derived from logistic regression analysis was 79.2% for reader 1 and 70.3% for reader 2.

Conclusions

CT imaging features including tumor attenuation and enhancement pattern can be useful to predict the biologic behavior of small ccRCC for adequate treatment strategy.