Effect of tin spectral filtration on organ and effective dose in CT colonography and CT lung cancer screening.

BACKGROUND: Studies of tin spectral filtration have demonstrated potential in reducing radiation dose while maintaining image quality for unenhanced computed tomography (CT) scans. The extent of dose reduction, however, was commonly measured using the change in the scanner's reported CTDIvol . This method does not account for how tin filtration affects patient organ and effective dose. PURPOSE: To investigate the effect of tin filtration on patient organ and effective dose for CT Lung Cancer Screening (LCS) and CT Colonography (CTC). METHODS: A previously-developed Monte Carlo program was adapted to model a 96-row CT scanner (Somatom Force, Siemens Healthineers) with tin filtration capabilities at 100 kV (100Sn) and 150 kV (150Sn). The program was then validated using experimental CTDIvol measurements at all available kV (70-150 kV) and tin-filtered kV options (100Sn and 150Sn). After validation, the program simulated LCS scans of the chest and CTC scan of the abdomen-pelvis for a population of 53 computational patient models from the extended cardiac-torso family. Each scan was performed using three different spectra: 120 kV, 100Sn, and 150Sn. CTDIvol -normalized organ doses and DLP-normalized effective doses, commonly referred to as dose conversion factors, were compared between the different spectra. RESULTS: For all LCS and CTC scans, CTDIvol -normalized organ doses and DLP-normalized effective doses increased with increasing beam hardness (120 kV, 100Sn, 150 Sn). For LCS, relative for 120 kV, conversion factors for 100Sn produced a median increase in effective dose of 9%, with organ dose increases of 8% to lung, 5% to breast, 15% to thyroid, and 3% to skin. Conversion factors for 150Sn produced a median increase in effective dose of 20%, with organ dose increases of 16%, 18%, 26%, and 12% to these same organs, respectively. For CTC, relative for 120 kV, conversion factors for 100Sn produced a median increase in effective dose of 12%, with organ dose increases of 9% to colon, 10% to liver, 11% to stomach, and 4% to skin. Conversion factors for 150Sn produced a median increase in effective dose of 21%, with organ dose increases of 16%, 17%, 19%, and 10% to these same organs, respectively. CONCLUSIONS: Results show that dose conversion factors are greater when using tin filtration and should be considered when evaluating tin's potential for dose reduction.

Impact of X-Ray Exposure From Computed Tomography on Wearable Insulin Delivery Devices.

BACKGROUND: To investigate the impact of radiation exposure from a computed tomography (CT) scanner on the functional integrity of a wearable insulin delivery system. METHODS: A total of 160 Omnipods and four personal diabetes managers (PDMs) were evenly divided into four groups: (1) control group (no radiation exposure), (2) typical radiation exposure group, (3) 4× typical radiation exposure group, and (4) scatter radiation group. Pods were attached to an anthropomorphic torso phantom on the abdomen (direct irradiation) or shoulder (scatter radiation) region. A third-generation dual-source CT scanner was used to scan the pods using either a typical exposure (used for routine CT abdominal study of a median size patient) or 4× typical exposure. A manufacturer-recommended 20-step functionality test was performed for all 160 Omnipods. RESULTS: The radiation dose (measured in volume CT Dose index) was 16 mGy for a typical exposure, and 64 mGy for 4× typical exposure. The scatter radiation is less than 0.1 mGy. All Pods passed the functionality test except one pod in the scatter radiation group, which sounded an alarm due to occlusion. The blockage to the fluid was due to a kink in the soft cannula, a mechanical issue not caused by the radiation exposure. CONCLUSIONS: This study suggests X-ray exposure levels used in radiological imaging procedures do not negatively impact the functional integrity of Omnipods. This finding may support the potential for the manufacturer to remove the warning that patients should remove the Pod for X-ray imaging procedures, which will have a huge impact on patient care.

Technical note: Relationship between peak skin dose and fluoroscopic Ka,r : Clinical variations and application in establishing substantial radiation dose levels.

BACKGROUND: The reference point cumulative air kerma (Ka,r ) is a commonly used dose quantity for establishing substantial radiation dose levels (SRDLs) that can provide guidance for patient dose management actions following fluoroscopically guided procedures. However, the Ka,r may not correlate well with the patient peak skin dose (Dskin,max ) because the relationship between Ka,r and Dskin,max may vary widely due to clinical variations. Therefore, it may be prudent for institutions to establish different Ka,r -based SRDL values based on the clinical procedure type. PURPOSE: The present study investigates the relationship between Ka,r and Dskin,max for different clinical services and how that variation may overestimate or underestimate the need for patient follow-up. Additionally, the study suggests a possible framework for establishing Ka,r SRDLs based on the clinical data analysis. METHODS: A retrospective analysis was performed for fluoroscopically guided interventions exceeding 5 Gy Ka,r . For each procedure, the patient Dskin,max was estimated and the ratio of Dskin,max to Ka,r (DKR) was calculated. Results were pooled into one of three clinical service categories: body interventions (n = 33), cardiac interventions (n = 81), or neurological (neuro) interventions (n = 44). The distributions in Ka,r , Dskin,max , and DKR were analyzed in aggregate and by the clinical service category. RESULTS: The median Ka,r values for procedures exceeding 5 Gy were 6.0 Gy (95% CI [5.6, 6.4]) for body interventions, 5.8 Gy (95% CI [5.5, 6.0]) for cardiac interventions, and 6.3 Gy (95% CI [5.9, 6.6]) for neuro interventions. Dskin,max for the same procedure data sets were 5.0 Gy (95% CI [4.4, 5.6]) for body interventions, 5.5 Gy (95% CI [5.2, 5.8]) for cardiac interventions, and 3.7 Gy (95% CI [3.4, 4.0]) for neuro interventions. This resulted in median DKR values of 0.81 for body interventions, 0.91 for cardiac interventions, and 0.59 for neuro interventions. CONCLUSIONS: This study illustrates the need to understand the relationship between the reported Ka,r and the patient Dskin,max for different types of interventional procedures. This is especially important when an institution uses Ka,r as the parameter for establishing an SRDL threshold to identify patients who may require clinical follow-up. The implications of this research and a guide for how to implement these findings are elaborated on in the Discussion.

Combination immunotherapy induces distinct T-cell repertoire responses when administered to patients with different malignancies.

BACKGROUND: CTLA-4 blockade with ipilimumab is Food and Drug Administration-approved for melanoma as a monotherapy and has been shown to modulate the circulating T-cell repertoire. We have previously reported clinical trials combining CTLA-4 blockade with granulocyte-macrophage colony-stimulating factor (GM-CSF) in metastatic melanoma patients and in metastatic castration resistant prostate cancer (mCRPC) patients. Here, we investigate the effect that cancer type has on circulating T cells in metastatic melanoma and mCRPC patients, treated with ipilimumab and GM-CSF. METHODS: We used next-generation sequencing of T-cell receptors (TCR) to compare the circulating T cells of melanoma and mCRPC patients receiving the same treatment with ipilimumab and GM-CSF by Wilcoxon rank sum test. Flow cytometry was utilized to investigate specific T-cell populations. TCR sequencing results were correlated with each T-cell subpopulation by Spearman's rank correlation coefficient. Of note, 14 metastatic melanoma patients had samples available for TCR sequencing and 21 had samples available for flow cytometry analysis; 37 mCRPC patients had samples available for sequencing of whom 22 have TCR data available at both timepoints; 20 of these patients had samples available for flow cytometry analysis and 16 had data available at both timepoints. RESULTS: While melanoma and mCRPC patients had similar pretreatment circulating T-cell counts, treatment induces greater expansion of circulating T cells in melanoma patients. Metastatic melanoma patients have a higher proportion of clones that increased more than fourfold after the treatment compared with mCRPC patients (18.9% vs 11.0%, p=0.017). Additionally, melanoma patients compared with mCRPC patients had a higher ratio of convergent frequency (1.22 vs 0.60, p=0.012). Decreases in clonality induced by treatment are associated with baseline CD8+ T-cell counts in both patient groups, but are more pronounced in the melanoma patients (r=-0.81, p<0.001 vs r=-0.59, p=0.02). TRIAL REGISTRATION NUMBERS: NCT00064129; NCT01363206.

Synthesis and Preliminary Antimicrobial Analysis of Isatin-Ferrocene and Isatin-Ferrocenyl Chalcone Conjugates.

In this study, we outline the synthesis of isatin-ferrocenyl chalcone and 1H-1,2,3-triazole-tethered isatin-ferrocene conjugates along with their antimicrobial evaluation against the human mucosal pathogen Trichomonas vaginalis. The introduction of a triazole ring among the synthesized conjugates improved the activity profiles with most of the compounds in the library, exhibiting 100% growth inhibition in a preliminary susceptibility screen at 100 µM. IC50 determination of the most potent compounds in the set revealed an inhibitory range between 2 and 13 µM. Normal flora microbiome are unaffected by these compounds, suggesting that these may be new chemical scaffolds for the discovery of new drugs against trichomonad infections.

Immune Toxicities Elicted by CTLA-4 Blockade in Cancer Patients Are Associated with Early Diversification of the T-cell Repertoire.

While immune checkpoint blockade elicits efficacious responses in many patients with cancer, it also produces a diverse and unpredictable number of immune-related adverse events (IRAE). Mechanisms driving IRAEs are generally unknown. Because CTLA-4 blockade leads to proliferation of circulating T cells, we examined in this study whether ipilimumab treatment leads to clonal expansion of tissue-reactive T cells. Rather than narrowing the T-cell repertoire to a limited number of clones, ipilimumab induced greater diversification in the T-cell repertoire in IRAE patients compared with patients without IRAEs. Specifically, ipilimumab triggered increases in the numbers of clonotypes, including newly detected clones and a decline in overall T-cell clonality. Initial broadening in the repertoire occurred within 2 weeks of treatment, preceding IRAE onset. IRAE patients exhibited greater diversity of CD4+ and CD8+ T cells, but showed no differences in regulatory T-cell numbers relative to patients without IRAEs. Prostate-specific antigen responses to ipilimumab were also associated with increased T-cell diversity. Our results show how rapid diversification in the immune repertoire immediately after checkpoint blockade can be both detrimental and beneficial for patients with cancer. Cancer Res; 77(6); 1322-30. ©2016 AACR.

Imaging strategies for assessing cartilage composition in osteoarthritis.

Efforts to reduce the ever-increasing rates of osteoarthritis (OA) in the developed world require the ability to non-invasively detect the degradation of joint tissues before advanced damage has occurred. This is particularly relevant for damage to articular cartilage because this soft tissue lacks the capacity to repair itself following major damage and is essential to proper joint function. While conventional magnetic resonance imaging (MRI) provides sufficient contrast to visualize articular cartilage morphology, more advanced imaging strategies are necessary for understanding the underlying biochemical composition of cartilage that begins to break down in the earliest stages of OA. This review discusses the biochemical basis and the advantages and disadvantages associated with each of these techniques. Recent implementations for these techniques are touched upon, and future considerations for improving the research and clinical power of these imaging technologies are also discussed.

The UF Family of hybrid phantoms of the pregnant female for computational radiation dosimetry.

Efforts to assess in utero radiation doses and related quantities to the developing fetus should account for the presence of the surrounding maternal tissues. Maternal tissues can provide varying levels of protection to the fetus by shielding externally-emitted radiation or, alternatively, can become sources of internally-emitted radiation following the biokinetic uptake of medically-administered radiopharmaceuticals or radionuclides located in the surrounding environment--as in the case of the European Union's SOLO project (Epidemiological Studies of Exposed Southern Urals Populations). The University of Florida had previously addressed limitations in available computational phantom representation of the developing fetus by constructing a series of hybrid computational fetal phantoms at eight different ages and three weight percentiles. Using CT image sets of pregnant patients contoured using 3D-DOCTOR(TM), the eight 50th percentile fetal phantoms from that study were systematically combined in Rhinoceros(TM) with the UF adult non-pregnant female to yield a series of reference pregnant female phantoms at fetal ages 8, 10, 15, 20, 25, 30, 35 and 38 weeks post-conception. Deformable, non-uniform rational B-spline surfaces were utilized to alter contoured maternal anatomy in order to (1) accurately position and orient each fetus and surrounding maternal tissues and (2) match target masses of maternal soft tissue organs to reference data reported in the literature.