Bioselective and Radiopaque Zinc-Biopolymeric Complex-Based Porous Biomaterials Promote Mammalian Tissue Ingrowth In Vivo While Inhibiting Microbial Biofilm Gene Expression and Biofilm Formation.

Metal-organic complexes have shown astounding bioactive properties; however, they are rarely explored as biomaterials. Recent studies showed that carboxymethyl-chitosan (CMC) genipin-conjugated zinc biomimetic scaffolds have unique bioselective properties. The biomaterial was reported to be mammalian cell-friendly; at the same time, it was found to discourage microbial biofilm formation on its surface, which seemed to be a promising solution to addressing the problem of trauma-associated biofilm formation and development of antimicrobial resistance. However, the mechanically frail characteristics and zinc overload raise concerns and limit the potential of the said biomaterials. Hence, the present work is focused on improving the strength of the earlier scaffold formulations, testing its in vivo efficacy and reaffirming its action against biofilm-forming microbe Staphylococcus aureus. Scaling up of CMC proportion increased rigidity, and 8% CMC was found to be the ideal concentration for robust scaffold fabrication. Freeze-dried CMC scaffolds with or without genipin (GP) cross-linking were conjugated with zinc using 2 M zinc acetate solution. Characterization results indicated that the CMC-Zn scaffolds, without genipin, showed mechanical properties close to bone fillers, resist in vitro enzymatic degradation until 4 weeks, are porous in nature, and have radiopacity close to mandibular bones. Upon implantation in a subcutaneous pocket of Wistar rats, the scaffolds showed tissue in-growth with simultaneous degradation without any signs of toxicity past 28 days. Neither were there any signs of toxicity in any of the vital organs. Considering many superior properties among the other formulations, the CMC-Zn scaffolds were furthered for biofilm studies. CMC-Zn showed negligible S. aureus biofilm formation on its surface as revealed by an alamar blue-based study. RT-PCR analysis revealed that CMC-Zn downregulated the expression of pro-biofilm effector genes such as icaC and clfB. A protein docking study predicted the inhibitory mechanism of CMC-Zn. Although it binds strongly when alone, at high density, it may cause inactivation of the transmembrane upstream activators of the said genes, thereby preventing their dimerization and subsequent inactivation of the effector genes. In conclusion, zinc-conjugated carboxymethyl-chitosan scaffolds are mechanically robust, porous, yet biodegradable, harmless to the host in the long term, they are radiopaque and prevent biofilm gene expression in notorious microbes; hence, they could be a suitable candidate for bone filler applications.

Leaf open time sinogram (LOTS): a novel approach for patient specific quality assurance of total marrow irradiation.

There is no ideal detector-phantom combination to perform patient specific quality assurance (PSQA) for Total Marrow (TMI) and Lymphoid (TMLI) Irradiation plan. In this study, 3D dose reconstruction using mega voltage computed tomography detectors measured Leaf Open Time Sinogram (LOTS) was investigated for PSQA of TMI/TMLI patients in helical tomotherapy. The feasibility of this method was first validated for ten non-TMI/TMLI patients, by comparing reconstructed dose with (a) ion-chamber (IC) and helical detector array (ArcCheck) measurement and (b) planned dose distribution using 3Dγ analysis for 3%@3mm and dose to 98% (D98%) and 2% (D2%) of PTVs. Same comparison was extended for ten treatment plans from five TMI/TMLI patients. In all non-TMI/TMLI patients, reconstructed absolute dose was within ± 1.80% of planned and IC measurement. The planned dose distribution agreed with reconstructed and ArcCheck measured dose with mean (SD) 3Dγ of 98.70% (1.57%) and 2Dγ of 99.48% (0.81%). The deviation in D98% and D2% were within 1.71% and 4.10% respectively. In all 25 measurement locations from TMI/TMLI patients, planned and IC measured absolute dose agreed within ± 1.20%. Although sectorial fluence verification using ArcCHECK measurement for PTVs chest from the five upper body TMI/TMLI plans showed mean ± SD 2Dγ of 97.82% ± 1.27%, the reconstruction method resulted poor mean (SD) 3Dγ of 92.00% (± 5.83%), 64.80% (± 28.28%), 69.20% (± 30.46%), 60.80% (± 19.37%) and 73.2% (± 20.36%) for PTVs brain, chest, torso, limb and upper body respectively. The corresponding deviation in median D98% and D2% of all PTVs were < 3.80% and 9.50%. Re-optimization of all upper body TMI/TMLI plans with new pitch and modulation factor of 0.3 and 3 leads significant improvement with 3Dγ of 100% for all PTVs and median D98% and D2% < 1.6%. LOTS based PSQA for TMI/TMLI is accurate, robust and efficient. A field width, pitch and modulation factor of 5 cm, 0.3 and 3 for upper body TMI/TMLI plan is suggested for better dosimetric outcome and PSQA results.

Dosimetric Effect of Rotational Setup Errors in Single-Isocenter Volumetric-Modulated Arc Therapy of Multiple Brain Metastases.

AIM: The aim of this study is to investigate the dosimetric effects of rotational uncertainties in patient positioning on target coverage in stereotactic radiosurgery (SRS) of multiple brain metastases using single isocenter volumetric modulated arc therapy (VMAT). MATERIALS AND METHODS: Ten SRS cases with multiple brain metastases (2-8) planned with single isocenter non-coplanar VMAT technique were investigated in this study. Pitch, yaw and roll displacements of 1, 3 and 5° were simulated about isocenter along each axes and nine plans were obtained for each case. Gross tumor volume (GTV) coverage obtained on simulated plans were compared with the original plan on four metrics of mean dose (Dmean), minimum dose to GTV (Dmin), dose to 95% of GTV (D95) and the volume covered by the 95% of the prescribed dose (V95). RESULTS: At 1° rotation about 4% of the PTV had V95 and D95 values <95%. The minimum dose obtained across all PTV was 85.1% and there was not much change in the mean dose values obtained. The PTV volume which had V95 and D95 values <95% were in the range of 0.05 - 0.07cc and at a radial distance of 6.2 cm - 7.2 cm. At 3° rotation almost 50% of the PTV had V95 and D95 values <95%. The minimum dose obtained across all PTV was 48.3% and the mean dose reduced to as low as 78.8%. At 5° rotation almost 74% of the PTV had V95 and D95 values <95%. The minimum dose obtained across all PTV was 21.2% and the mean dose reduced to as low as 49.2%. CONCLUSION: Our results indicate that correcting rotational uncertainties is critical in single-isocenter, multi-target SRS. For rotational deviations, radial distance of the target from isocenter along the respective axis has a strong influence on target coverage. For rotational setup deviation at a given radial distance larger targets tend to have lesser geometric miss compared to smaller targets. Mathematical model for spherical targets can be used to estimate V95 for given rotational errors.

The "Skipped Segment Screw" Construct: An Alternative to Conventional Lateral Mass Fixation-Biomechanical Analysis in a Porcine Cervical Spine Model.

STUDY DESIGN: Cadaveric biomechanical study. PURPOSE: We compared the "skipped segment screw" (SSS) construct with the conventional "all segment screw" (ASS) construct for cervical spine fixation in six degrees of freedom in terms of the range of motion (ROM). OVERVIEW OF LITERATURE: Currently, no clear guidelines are available in the literature for the configuration of lateral mass (LM) screwrod fixation for cervical spine stabilization. Most surgeons tend to insert screws bilaterally at all segments from C3 to C6 with the assumption that implants at every level will provide maximum stability. METHODS: Six porcine cervical spine specimens were harvested from fresh 6-9-month-old pigs. Each specimen was sequentially tested in the following order: intact uninstrumented (UIS), SSS (LM screws in C3, C5, and C7 bilaterally), and ASS (LM screws in C3-C7 bilaterally). Biomechanical testing was performed with a force of 2 Nm in six degrees of freedom and 3D motion tracking was performed. RESULTS: The two-tailed paired t-test was used for statistical analysis. There was a significant decrease in ROM in instrumented specimens compared with that in UIS specimens in all six degrees of motion (p<0.05), whereas there was no significant difference in ROM between the different types of constructs (SSS and ASS). CONCLUSIONS: Because both configurations provide comparable stability under physiological loading, we provide a biomechanical basis for the use of SSS configuration owing to its potential clinical advantages, such as relatively less bulk of implants within a small operative field, relative ease of manipulating the rod into position, shorter surgical time, less blood loss, lower risk of screw-related complications, less implant-related costs, and most importantly, no compromise in the required stability needed until fusion.

Verification of Dosimetric Commissioning Accuracy of Intensity Modulated Radiation Therapy and Volumetric Modulated Arc Therapy Delivery using Task Group-119 Guidelines.

AIM: The purpose of this study is to verify the accuracy of the commissioning of intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) based on the recommendation of the American Association of Physicists in Medicine Task Group 119 (TG-119). MATERIALS AND METHODS: TG-119 proposes a set of clinical test cases to verify the accuracy of IMRT planning and delivery system. For these test cases, we generated two sets of treatment plans, the first plan using 7-9 IMRT fields and a second plan utilizing two-arc VMAT technique for both 6 MV and 15 MV photon beams. The template plans of TG-119 were optimized and calculated by Varian Eclipse Treatment Planning System (version 13.5). Dose prescription and planning objectives were set according to the TG-119 goals. The point dose (mean dose to the contoured chamber volume) at the specified positions/locations was measured using compact (CC-13) ion chamber. The composite planar dose was measured with IMatriXX Evaluation 2D array with OmniPro IMRT Software (version 1.7b). The per-field relative gamma was measured using electronic portal imaging device in a way similar to the routine pretreatment patient-specific quality assurance. RESULTS: Our planning results are compared with the TG-119 data. Point dose and fluence comparison data where within the acceptable confident limit. CONCLUSION: From the obtained data in this study, we conclude that the commissioning of IMRT and VMAT delivery were found within the limits of TG-119.

Comparison of Head Scatter Factor for 6MV and 10MV flattened (FB) and Unflattened (FFF) Photon Beam using indigenously Designed Columnar Mini Phantom.

To measure and compare the head scatter factor for flattened (FB) and unflattened (FFF) of 6MV and 10MV photon beam using indigenously designed mini phantom. A columnar mini phantom was designed as recommended by AAPM Task Group 74 with low and high atomic number materials at 10 cm (mini phantom) and at approximately twice the depth of maximum dose water equivalent thickness (brass build-up cap). Scatter in the accelerator (Sc) values of 6MV-FFF photon beams are lesser than that of the 6MV-FB photon beams (0.66-2.8%; Clinac iX, 2300CD) and (0.47-1.74%; True beam) for field sizes ranging from 10 × 10 cm(2) to 40 × 40 cm(2). Sc values of 10MV-FFF photon beams are lesser (0.61-2.19%; True beam) than that of the 10MV-FB photons beams for field sizes ranging from 10 × 10 cm(2) to 40 × 40 cm(2). The SSD had no influence on head scatter for both flattened and unflattened beams and irrespective of head design of the different linear accelerators. The presence of field shaping device influences the Sc values. The collimator exchange effect reveals that the opening of the upper jaw increases Sc irrespective of FB or FFF photon beams and different linear accelerators, and it is less significant in FFF beams. Sc values of 6MV-FB square field were in good agreement with that of AAPM, TG-74 published data for Varian (Clinac iX, 2300CD) accelerator. Our results confirm that the removal of flattening filter decreases in the head scatter factor compared to flattened beam. This could reduce the out-of-field dose in advanced treatment delivery techniques.