MRI Contrast Agents: Developments, Challenges, and Future Trends

Contrast agents in medicine are chemical materials used to improve tissue and fluid contrast in the body during medical imaging. It is mainly used in improving the visibility of blood vessels and the gastrointestinal tract. Some types of contrast materials are used in a medical imaging examination and can be classified according to the imaging technique used. The first contract agent dates back to 1988 which is called gadopentetate dimeglumine (Magnevist®) and was allocated for Magnetic Resonance Imaging (MRI). Then, I has become available in clinical use. Afterwards, many studies have examined the capability of MRI contrast agents to be used in diagnostic imaging in all parts of the body including the skin, the central nervous system, heart and circulation, breast, lungs, musculoskeletal and lymphatic systems, and even the gastrointestinal tract. Nowadays, MRI contrast agents are widely used in clinical practice and have expanded beyond the imitational expectations to be a key tool in disease diagnosis around the world. Contrast-Enhanced (CE) MRI keeps in development and new technologies have emerged and new agents were introduced, with great opportunity being provided to ensure better imaging and patient management practices. Also, new clinical challenges were associated with the progress in CE-MRI. This paper aims to overview the historical development of MRI and contrast materials in order to shed light on the clinical development of CE-MRI. Also, the paper overviews the contemporary perspectives and clinical challenges associated with CE-MRI with the provision of significant future trends

The Epidemiology and Outcome of Biliary Atresia: Saudi Arabian National Study (2000–2018)

BackgroundThe epidemiology and outcomes of biliary atresia (BA) have been well-documented in national cohorts from two main ethnicities, namely, the Asian Orientals and Caucasians, with incidence ranging from 1 in 5,000 to 1 in 9,000 live births in East Asia and 1 in 15,000 to 19,000 live births in Europe and North America.ObjectiveWe report the first nationwide BA study outside North America, Europe, and East Asia to describe the epidemiology and outcomes of BA in Saudi Arabia.MethodsA national database of BA cases diagnosed between 2000 and 2018 was analyzed. We assessed clearance of jaundice (bilirubin <20 μmol/L) in all cases that underwent Kasai portoenterostomy (KPE). We then estimated survival using the Kaplan–Meier method with endpoints of liver transplantation (LT), death, or survival with native liver (SNL).ResultsBA was diagnosed in 204 infants (106 females; 10% pre-term). The incidence of BA was 1 in 44,365, or 2.254 in 100,000 live births (range, 0.5–4 in 100,000). Polysplenia was diagnosed in 22 cases (11%). The median age at referral was 65 days. A total of 146 children (71.5%) underwent KPE at a median age of 70 days. Clearance of jaundice was achieved in 66 of the 146 (45%) infants. The 10-year SNL after KPE was 25.5%, and the overall 10-year estimated survival was 72.5%. The Kaplan–Meier survival curves for patients undergoing KPE at the age of <60, 61–90, and >90 days showed a SNL rate at 51.6, 33, and 12.5%, respectively, at 5 years (P < 0.001). The 2-, 5-, and 10-year post-LT survival rates were 92.5, 90.6, and 90%, respectively. Undergoing an initial KPE did not impact negatively on the overall LT survival rate when compared to BA cases that underwent primary LT (P = 0.88).ConclusionThe incidence rate of BA in Saudi Arabia is lower than the incidence reported elsewhere. Late referral of BA cases remains a problem in Saudi Arabia; as a result, the SNL rate was lower than reported by other national registries. Hence, national policies devoted to timely referral and earlier age at KPE are needed

MOSFET annealing and interface dosimetry in contemporary radiation therapy

[Background and Purpose] In-vivo, skin, and interface dosimetry in modern radiation therapy is an important issue that demands a reliable radiation dosimeter capable of measuring skin doses. The Metal Oxide Semiconductor Field Effect Transistor “MOSFET” dosimeter became popular as a radiation dosimeter in radiation therapy and one of its recently designed versions for skin dosimetry, called MOSkin, has become very popular. Unfortunately MOSFET has a limited lifespan due to a saturated build up of positive charges in its sensitive dosimetric volume - gate oxide, which is mainly located near the Silicon- Silicon dioxide (Si-SiO2) interface. This built up charge reduces its sensitivity, linearity, and stability. The aims of this thesis are an investigation of MOSkin™, with the possibility of annealing the MOSFET dosimeter designed by the Centre for Medical Radiation Physics, and being able to re-use it again after multiple cycles of irradiation and annealing. Virgin and annealed MOSkin detectors have been reused in addition to an Attix chamber, a Monte Carlo simulation, and EBT2 films to verify a newly developed radiotherapy treatment planning algorithm (TPA), the Acuros® XB (Varian, Palo Alto, CA). This verification covered dose predictions in the areas with strong electronic disequilibrium such as the build-up region and interfaces inside the phantom such as tissue – air, tissue – lung, and tissue – steel. The current clinical treatment planning algorithm (TPA), the Anisotropic Analytical Algorithm AAA (Varian, Palo Alto, CA) was verified experimentally in comparison to the Acuros® XB. [Materials and Methods] Groups of MOSkin detectors were irradiated with different doses on a 6 MV X-ray beam from a medical linear accelerator (LINAC) and then annealed using different annealing methods. Ultraviolet (UV) light with 4.92 eV mono-energetic photons from a filtered Mercury vapour lamp was used for UV annealing, while isothermal annealing was carried out in the furnace heated to a temperature of 1500C. Direct electric current (DC) was also used to anneal MOSkin with a current ranging from 5 mA to 15 mA, and pulsed electric current was used for current annealing with a current ranging 50- 300mA per pulse. The annealing time required to recover the threshold voltage (Vth) varied for each type of annealing, so the parameters influent on this were studied. The annealed MOSkin detectors were irradiated again to check their sensitivities, linearity, and signal stability. The cycles of annealing and irradiation for each group of MOSkin were repeated many times to investigate the effectiveness of each annealing method. To verify and benchmark the treatment planning algorithms, MOSkin and Attix ionising chambers were used to verify the dose calculated by the Acuros® XB, and the AAA at the build-up region for 6 MV and 18 MV X-ray photon beams with field sizes of 4 cm x 4 cm, 10 cm x 10 cm, and 40 cm x 40 cm, under a normal incidence X-ray beam from linear accelerator (LINAC). To check the performance of treatment planning systems (TPSs) for dose calculations under an oblique beam, experiments with a 45˚ beam incidence and 10 cm x 10 cm field size with 6 MV and 18 MV X-ray photons beams were carried out. For interface dosimetry, MOSkin and EBT2 films were used to measure doses near the air, steel, and lung interfaces, as well as using Monte Carlo simulations with 6 MV and 18 MV photon beams and 10 cm x 10 cm field sizes, for all but the lung cases, with a small 3 cm x 3 cm field size. [Results] The annealing methods that were investigated revealed different clinical outcomes. UV light was able to recover the threshold voltage but not the sensitivity with essential MOSkin Vth instability (within ±28 mV). Isothermal annealing was a good alternative in that it fully recovered the sensitivity and threshold voltage with an acceptable signal instability (±4 mV). DC annealing was shown to be much better than UV and isothermal annealing provided full recovery of sensitivity, threshold voltage linearity dose response, and excellent stability within ±1 mV. Pulsed current annealing was the best annealing method of all, with full recovery of the sensitivity, threshold voltage dose response linearity, and excellent stability ±1 mV. Dosimetry in the build-up region resulted in an excellent agreement between MOSkin and Attix (within ±2%), although Acuros® XB was much better than AAA in all the setups used. For interface dosimetry, Acuros® XB performed better than AAA near the interfaces, although it had some slight shift in depth dose distribution within 2 mm of the proximal and distal interfaces, for all cases except the lung. With the lung case, Acuros® XB and AAA performed satisfactorily and agreed with the Monte Carlo simulated doses within ±5%. [Conclusions] Direct current annealing (DC) and pulsed current annealing are the best annealing techniques for a MOSkin dosimeter. This will have potential benefits for MOSFET applications in medicine and space dosimetry, especially for departments with limited budgets, and in developing countries. The verification of Acuros® XB showed that this TPA performed much better than previous TPA and AAA, and it was very close to the MC simulation and experimental measurements. As an application for the annealing procedure, pulsed current annealing was used with build-up measurements. The total doses during the experiments for build-up and interfaces dosimetry were 230 and 185 Gy, respectively. It has been shown that two periodically annealed MOSkins detectors were enough for all the build-up measurements, while for doses on interface dosimetry measurements, the 11 virgin MOSkins that were used clearly showed the benefits of the annealing technique developed for MOSkin dosimeters for clinical applications

Direct and pulsed current annealing of p-MOSFET based dosimeter: The MOSkin

Contemporary radiation therapy (RT) is complicated and requires sophisticated real-time quality assurance (QA). While 3D real-time dosimetry is most preferable in RT, it is currently not fully realised. A small, easy to use and inexpensive point dosimeter with real-time and in vivo capabilities is an option for routine QA. Such a dosimeter is essential for skin, in vivo or interface dosimetry in phantoms for treatment plan verification. The metal-oxide-semiconductor-field-effect-transistor (MOSFET) detector is one of the best choices for these purposes, however, the MOSFETs sensitivity and its signal stability degrade after essential irradiation which limits its lifespan. The accumulation of positive charge on the gate oxide and the creation of interface traps near the silicon-silicon dioxide layer is the primary physical phenomena responsible for this degradation. The aim of this study is to investigate MOSFET dosimeter recovery using two proposed annealing techniques: direct current (DC) and pulsed current (PC), both based on hot charged carrier injection into the gate oxide of the p-MOSFET dosimeter. The investigated MOSFETs were reused multiple times using an irradiation-annealing cycle. The effect of the current-annealing parameters was investigated for the dosimetric characteristics of the recovered MOSFET dosimeters such as linearity, sensitivity and initial threshold voltage. Both annealing techniques demonstrated excellent results in terms of maintaining a stable response, linearity and sensitivity of the MOSFET dosimeter. However, PC annealing is more preferable than DC annealing as it offers better dose response linearity of the reused MOSFET and has a very short annealing time

Quality assurance of Cyberknife robotic stereotactic radiosurgery using an angularly independent silicon detector

Purpose: The aim of this work was to evaluate the use of an angularly independent silicon detector (edgeless diodes) developed for dosimetry in megavoltage radiotherapy for Cyberknife in a phantom and for patient quality assurance (QA). Method: The characterization of the edgeless diodes has been performed on Cyberknife with fixed and IRIS collimators. The edgeless diode probes were tested in terms of basic QA parameters such as measurements of tissue-phantom ratio (TPR), output factor and off-axis ratio. The measurements were performed in both water and water-equivalent phantoms. In addition, three patient-specific plans have been delivered to a lung phantom with and without motion and dose measurements have been performed to verify the ability of the diodes to work as patient-specific QA devices. The data obtained by the edgeless diodes have been compared to PTW 60016, SN edge, PinPoint ionization chamber, Gafchromic EBT3 film, and treatment planning system (TPS). Results: The TPR measurement performed by the edgeless diodes show agreement within 2.2% with data obtained with PTW 60016 diode for all the field sizes. Output factor agrees within 2.6% with that measured by SN EDGE diodes corrected for their field size dependence. The beam profiles\u27 measurements of edgeless diodes match SN EDGE diodes with a measured full width half maximum (FWHM) within 2.3% and penumbra widths within 0.148 mm. Patient-specific QA measurements demonstrate an agreement within 4.72% in comparison with TPS. Conclusion: The edgeless diodes have been proved to be an excellent candidate for machine and patient QA for Cyberknife reproducing commercial dosimetry device measurements without need of angular dependence corrections. However, further investigation is required to evaluate the effect of their dose rate dependence on complex brain cancer dose verification

Impact of Metformin on Periodontal and Peri-Implant Soft and Hard Tissue

Periodontal and peri-implant soft and hard tissue in diabetic patients have always been a topic of interest for researchers and clinicians alike. Among which, a subtopic that has attracted more attention is the beneficial effect of metformin (MF) on periodontal and peri-implant soft and hard tissue. This review aimed to assess the impact of MF on the periodontal and peri-implant soft- and hard-tissue healing among diabetic patients. Research was conducted using the keywords ‘metformin’, ‘diabetes’, ‘periodontitis’, ‘implant’, and ‘peri-implantitis’ via the Medline (PubMed) and Google Scholar databases. Selected articles were reviewed. A total of 21 articles, discussing the impact on periodontal health (six animal studies, seven clinical studies, and three systematic reviews) and five studies on peri-implant health (four animal studies and one clinical study) were included. All have reported a positive impact of MF on decreasing the inflammatory response, oxidative stress, and ultimate bone loss. Similarly, human studies reported a positive effect of MF on clinical and radiographic parameters compared with controls. Despite systematic reviews reporting heterogeneity among the included studies, MF has shown a positive impact on periodontal health. In animal, clinical studies, and systematic reviews, MF showed a protective impact on periodontal and peri-implant health

Comparative evaluation of modern dosimetry techniques near low- and high-density heterogeneities

The purpose of this study is to compare performance of several dosimetric methods in heterogeneous phantoms irradiated by 6 and 18 MV beams. Monte Carlo (MC) calculations were used, along with two versions of Acuros XB, anisotropic analytical algorithm (AAA), EBT2 film, and MOSkin dosimeters. Percent depth doses (PDD) were calculated and measured in three heterogeneous phantoms. The first two phantoms were a 30 x 30 x 30 cm3 solid-water slab that had an air-gap of 20x 2.5 x 2.35 cm3. The third phantom consisted of 30 x 30 x 5 cm3 solid water slabs, two 30 x 30 x 5 cm3 slabs of lung, and one 30 x 30 x 1 cm3 solid water slab. Acuros XB, AAA, and MC calculations were within 1% in the regions with particle equilibrium. At media interfaces and buildup regions, differences between Acuros XB and MC were in the range of +4.4% to −12.8%. MOSkin and EBT2 measurements agreed to MC calculations within ~ 2.5%, except for the first centimeter of buildup where differences of 4.5% were observed. AAA did not predict the backscatter dose from the high-density heterogeneity. For the third, multilayer lung phantom, 6 MV beam PDDs calculated by all TPS algorithms were within 2% of MC. 18 MV PDDs calculated by two versions of Acuros XB and AAA differed from MC by up to 2.8%, 3.2%, and 6.8%, respectively. MOSkin and EBT2 each differed from MC by up to 2.9% and 2.5% for the 6 MV, and by −3.1% and ~2% for the 18 MV beams. All dosimetric techniques, except AAA, agreed within 3% in the regions with particle equilibrium. Differences between the dosimetric techniques were larger for the 18 MV than the 6 MV beam. MOSkin and EBT2 measurements were in a better agreement with MC than Acuros XB calculations at the interfaces, and they were in a better agreement to each other than to MC. The latter is due to their thinner detection layers compared to MC voxel sizes

SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Background: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population