Characterization of a flexible a-Si:H detector for in vivo dosimetry in therapeutic x-ray beams.

BACKGROUND: The increasing use of complex and high dose-rate treatments in radiation therapy necessitates advanced detectors to provide accurate dosimetry. Rather than relying on pre-treatment quality assurance (QA) measurements alone, many countries are now mandating the use of in vivo dosimetry, whereby a dosimeter is placed on the surface of the patient during treatment. Ideally, in vivo detectors should be flexible to conform to a patient's irregular surfaces. PURPOSE: This study aims to characterize a novel hydrogenated amorphous silicon (a-Si:H) radiation detector for the dosimetry of therapeutic x-ray beams. The detectors are flexible as they are fabricated directly on a flexible polyimide (Kapton) substrate. METHODS: The potential of this technology for application as a real-time flexible detector is investigated through a combined dosimetric and flexibility study. Measurements of fundamental dosimetric quantities were obtained including output factor (OF), dose rate dependence (DPP), energy dependence, percentage depth dose (PDD), and angular dependence. The response of the a-Si:H detectors investigated in this study are benchmarked directly against commercially available ionization chambers and solid-state diodes currently employed for QA practices. RESULTS: The a-Si:H detectors exhibit remarkable dose linearities in the direct detection of kV and MV therapeutic x-rays, with calibrated sensitivities ranging from (0.580 ± 0.002) pC/cGy to (19.36 ± 0.10) pC/cGy as a function of detector thickness, area, and applied bias. Regarding dosimetry, the a-Si:H detectors accurately obtained OF measurements that parallel commercially available detector solutions. The PDD response closely matched the expected profile as predicted via Geant4 simulations, a PTW Farmer ionization chamber and a PTW ROOS chamber. The most significant variation in the PDD performance was 5.67%, observed at a depth of 3 mm for detectors operated unbiased. With an external bias, the discrepancy in PDD response from reference data was confined to ± 2.92% for all depths (surface to 250 mm) in water-equivalent plastic. Very little angular dependence is displayed between irradiations at angles of 0° and 180°, with the most significant variation being a 7.71% decrease in collected charge at a 110° relative angle of incidence. Energy dependence and dose per pulse dependence are also reported, with results in agreement with the literature. Most notably, the flexibility of a-Si:H detectors was quantified for sample bending up to a radius of curvature of 7.98 mm, where the recorded photosensitivity degraded by (-4.9 ± 0.6)% of the initial device response when flat. It is essential to mention that this small bending radius is unlikely during in vivo patient dosimetry. In a more realistic scenario, with a bending radius of 15-20 mm, the variation in detector response remained within ± 4%. After substantial bending, the detector's photosensitivity when returned to a flat condition was (99.1 ± 0.5)% of the original response. CONCLUSIONS: This work successfully characterizes a flexible detector based on thin-film a-Si:H deposited on a Kapton substrate for applications in therapeutic x-ray dosimetry. The detectors exhibit dosimetric performances that parallel commercially available dosimeters, while also demonstrating excellent flexibility results.

Hydrogenated amorphous silicon high flux x-ray detectors for synchrotron microbeam radiation therapy.

Objective. Microbeam radiation therapy (MRT) is an alternative emerging radiotherapy treatment modality which has demonstrated effective radioresistant tumour control while sparing surrounding healthy tissue in preclinical trials. This apparent selectivity is achieved through MRT combining ultra-high dose rates with micron-scale spatial fractionation of the delivered x-ray treatment field. Quality assurance dosimetry for MRT must therefore overcome a significant challenge, as detectors require both a high dynamic range and a high spatial resolution to perform accurately.Approach. In this work, a series of radiation hard a-Si:H diodes, with different thicknesses and carrier selective contact configurations, have been characterised for x-ray dosimetry and real-time beam monitoring applications in extremely high flux beamlines utilised for MRT at the Australian Synchrotron.Results. These devices displayed superior radiation hardness under constant high dose-rate irradiations on the order of 6000 Gy s-1, with a variation in response of 10% over a delivered dose range of approximately 600 kGy. Dose linearity of each detector to x-rays with a peak energy of 117 keV is reported, with sensitivities ranging from (2.74 ± 0.02) nC/Gy to (4.96 ± 0.02) nC/Gy. For detectors with 0.8µm thick active a-Si:H layer, their operation in an edge-on orientation allows for the reconstruction of micron-size beam profiles (microbeams). The microbeams, with a nominal full-width-half-max of 50µm and a peak-to-peak separation of 400µm, were reconstructed with extreme accuracy. The full-width-half-max was observed as 55 ± 1µm. Evaluation of the peak-to-valley dose ratio and dose-rate dependence of the devices, as well as an x-ray induced charge (XBIC) map of a single pixel is also reported.Significance. These devices based on novel a-Si:H technology possess a unique combination of accurate dosimetric performance and radiation resistance, making them an ideal candidate for x-ray dosimetry in high dose-rate environments such as FLASH and MRT.

Safety and Effectiveness of Veno-Venous Extracorporeal Membrane Oxygenation Combined With Continuous Renal Replacement Therapy.

Patients receiving extracorporeal membrane oxygenation (ECMO) often suffer from acute kidney injury (AKI), requiring continuous renal replacement therapy (CRRT). In our clinical practice, we connected the inlet line of a CRRT machine to the postoxygenator Luer port and the outlet line to the inlet Luer port of the oxygenator. In this case series, we analyzed the interaction between the two machines. Between December 31, 2017, and December 31, 2019, we enrolled 15 patients from the ICU of the San Matteo Hospital, Pavia, Italy. All of them suffered from severe acute respiratory distress syndrome and AKI stage 3. We analyzed 570 hours of CRRT combined with venovenous ECMO and collected 261,751 CRRT data. No discontinuation of CRRT occurred before 48 hours. Most of the alarms occurred within 24 hours of the connection: 22/10,831 (0.2%) showed an outranged inlet pressure, 11/10831 (0.11%) showed an outranged transmembrane pressure, 14/10,831 (0.13%) showed an outranged inlet pressure, and 138/10,831 (1.27%) an outranged effluent pressure. The rate per minute set for the ECMO circuit was correlated with the inlet (ß = 5.38; CI, 95% 1.42-9.35; p = 0.008), transmembrane (ß = 4.6; CI, 95% 1.97-7.24; p = 0.001), effluent (ß = 3.02; CI, 95% 1.15-4.90; p = 0.002), and outlet pressures (ß = 597; CI, 95% 2.31-9.63; p = 0.001) of the CRRT circuit. We reported that our configuration could be safe and effective, however well-designed studies would be beneficial for determining the potential risks and benefits.

A Combined Hypofractionated Volumetric Modulated Arc Radiotherapy, Radio-Sensitising and Adjuvant Metronomic Chemotherapy Treatment for Canine Stage IV Nasal Tumours With Intracranial Extension.

Radiation therapy has become the standard of care in the treatment of canine intranasal neoplasia, but because of the poor prognosis associated with stage IV nasal tumours and the proximity of the brain to the irradiation target, few data regarding the treatment of very advanced neoplasms are available. The aim of this pilot study was to evaluate the feasibility, safety and effectiveness of a combined treatment composed of definitive high-dose hypofractionated volumetric modulated arc radiotherapy on tumours with concurrent treatment of regional lymph nodes if positive or as prophylaxis, carboplatin radio-sensitising, and adjuvant metronomic chemotherapy for stage IV canine nasal tumours with intracranial extension. A pilot observational study was conducted in 7 dogs. Magnetic resonance imaging follow-up examinations revealed complete responses in 5 dogs and partial responses in 2. The median overall survival time, evaluated via Kaplan-Meier survival analysis, was 310 days with a 95% confidence interval of 210-400 days, whereas the median progression-free survival was 240 days with a 95% confidence interval of 190-290 days. Despite the proximity of highly sensitive organs at risk, no grade III or IV toxicities were observed, and volumetric modulated arc radiotherapy seemed to be a feasible treatment option for stage IV canine nasal tumours where conformal 3D radiotherapy has proven to give higher doses with severe damage to the surrounding unaffected tissues. Further studies are needed on the role of the sphenoid bone microscopic infiltration and regional lymph node involvement. The absence of severe toxicity could also lead to a dose escalation study and chemotherapy scheme.

A simple prognostic score for COVID-19 hospitalized patients developing deep vein thrombosis.

OBJECTIVE: The aim of our study was to analyze the specificity, accuracy and sensitivity of a simple, easy to calculate, prognostic score for hospitalized COVID19 patients developing deep vein thrombosis. METHODS: From March 1st to April 28th, 942 COVID-19 patients with severe symptoms were admitted to the hospital San Matteo of Pavia-Italy. Thirty two patients (3.4%) developed deep vein thrombosis during hospitalization. In all patients hemostatic and inflammatory parameters were abnormal. A simple prognostic score was developed based on the presence of specific co morbidities and D-dimers levels (quick San Matthew Score-quick SMS). RESULTS: Nine patients died in a condition of multiple organ failure, 23 patients (71.9%) survived and left the hospital in good general conditions. The developed score was based simply on two parameters: 1) presence of four specific co morbidities and 2)systemic levels of D-Dimers. The quick San Matthew Score resulted in a sensitivity, specificity and overall accuracy of more than 90% (94%, 92%,93% respectively) and compared favorably with other scores. The score was prospectively validated in 100 COVID19 patients who developed deep vein thrombosis collected from the literature and prospectively confirmed in our hospital. CONCLUSIONS: The findings of our study underline the importance of an immediate aggressive therapeutic approach for moderate and high-risk patients with COVID19 infection. The quick SMS score may help to identify patients at high risk for mortality and to follow the clinical outcome of the patient. A simple, easy to calculate prognostic score may also facilitate communication among health workers.

A combined protocol with piroxicam, chemotherapy, and whole pelvic irradiation with simultaneous boost volumetric modulated arc radiotherapy for muscle-invasive canine urinary transitional cell carcinoma: First clinical experience.

The aims of this pilot study were to evaluate the feasibility and efficacy of high-dose hypofractionated volumetric modulated arc radiotherapy (VMAT) applied to whole pelvic region radiotherapy (WPRT) with multilevel simultaneous integrated boost (MLSIB) combined with piroxicam and chemotherapy for the treatment of canine transitional cell carcinoma (TCC) of the lower urinary tract with muscle invasion TCC. Twelve dogs were enrolled, according to stage, in two groups: group 1, TCC confined to the urinary tract; group 2, TCC with metastasis. The planning target volume dose was tailored from 36 to 42 Gy in 6 fractions. All dogs were prescribed piroxicam and radiosensitizing carboplatin, and six received chemotherapy after radiotherapy. Serial follow-ups with computed tomography and magnetic resonance imaging were performed. Disease control and toxicity effects were evaluated according to the Response Evaluation Criteria in Solid Tumors and Veterinary Radiation Therapy Oncology Group criteria. The treatment was well tolerated, and no high-grade side effects were reported. The median overall survival times for groups 1 and 2 were 1,230 and 150 days, respectively. A considerable percentage of patients in group1 (50%) were still alive at the time of writing this paper, and a longer follow-up could enable a more accurate survival analysis. This preliminary analysis shows that VMAT applied to the WPRT with MLSIB is an effective and safe option for dogs with lower urinary TCC, although the presence of metastases worsens the prognosis.

High dose hypofractionated frameless volumetric modulated arc radiotherapy is a feasible method for treating canine trigeminal nerve sheath tumors.

The aim of this prospective pilot study was to evaluate the feasibility and effectiveness of curative intent high dose hypofractionated frameless volumetric modulated arc radiotherapy for treatment of canine trigeminal peripheral nerve sheath tumors. Client-owned dogs with a presumptive imaging-based diagnosis of trigeminal peripheral nerve sheath tumor were recruited for the study during the period of February 2010 to December 2013. Seven dogs were enrolled and treated with high dose hypofractionated volumetric modulated arc radiotherapy delivered by a 6 MV linear accelerator equipped with a micro-multileaf beam collimator. The plans were computed using a Monte Carlo algorithm with a prescription dose of 37 Gy delivered in five fractions on alternate days. Overall survival was estimated using a Kaplan-Meier curve analysis. Magnetic resonance imaging (MRI) follow-up examinations revealed complete response in one dog, partial response in four dogs, and stable disease in two dogs. Median overall survival was 952 days with a 95% confidence interval of 543-1361 days. Volumetric modulated arc radiotherapy was demonstrated to be feasible and effective for trigeminal peripheral nerve sheath tumor treatment in this sample of dogs. The technique required few sedations and spared organs at risk. Even though larger studies are required, these preliminary results supported the use of high dose hypofractionated volumetric modulated arc radiotherapy as an alternative to other treatment modalities.

Volumetric Modulated Arc (Radio) Therapy in Pets Treatment: The "La Cittadina Fondazione" Experience.

Volumetric Modulated Arc Therapy (VMAT) is a modern technique, widely used in human radiotherapy, which allows a high dose to be delivered to tumor volumes and low doses to the surrounding organs at risk (OAR). Veterinary clinics takes advantage of this feature due to the small target volumes and distances between the target and the OAR. Sparing the OAR permits dose escalation, and hypofractionation regimens reduce the number of treatment sessions with a simpler manageability in the veterinary field. Multimodal volumes definition is mandatory for the small volumes involved and a positioning device precisely reproducible with a setup confirmation is needed before each session for avoiding missing the target. Additionally, the elaborate treatment plan must pursue hard constraints and objectives, and its feasibility must be evaluated with a per patient quality control. The aim of this work is to report results with regard to brain meningiomas and gliomas, trigeminal nerve tumors, brachial plexus tumors, adrenal tumors with vascular invasion and rabbit thymomas, in comparison with literature to determine if VMAT is a safe and viable alternative to surgery or chemotherapy alone, or as an adjuvant therapy in pets.

Stereotactic Volume Modulated Arc Radiotherapy in Canine Meningiomas: Imaging-Based and Clinical Neurological Posttreatment Evaluation.

A prospective study to assess high-dose hypofractionated volume modulated arc radiotherapy feasibility and efficacy in canine meningiomas was conducted. Thirty-nine patients with encephalic and spinal meningiomas assumed from MRI findings were recruited and received high-dose hypofractionated volumetric modulated arc radiotherapy by a linear accelerator equipped with an external beam modulator micro-multileaf collimator and an XVI cone beam computed tomography system. The prescribed mean dose was 33 Gy in five fractions. The treatment feasibility was tested through planned and delivered dose agreement checks. Regular clinical examinations were performed during and after irradiation time, with regard to mentation, deambulation, cranial nerve dysfunction, and seizures. Serial MRI exams were done 60 days after irradiation and after 4, 6, 12, 18, and 24 mo. Volumetric disease reduction criteria implemented with clinical neurological systematic evaluation were adopted to assess the course and to categorize patients' responses. Complete and partial responses were observed on the whole in 65.5% of alive patients 24 mo after irradiation. Two-yr overall and disease-specific survival rates were 74.3% and 97.4%, respectively, and the putative radiotoxic effects were found to be few and slight.

Computed tomography, magnetic resonance imaging and a novel surgical approach of atlanto-axial instability with incongruence in dogs.

Atlanto-axial (AA) instability due to ligament insufficiency is a common cause of cervical spinal cord compression in toy breeds. However, in some dogs a difference in size between the atlas and the axis leads to joint incongruence that exacerbates AA subluxation and makes surgical treatment challenging. Twelve dogs with AA instability with incongruence were enrolled in a single institution prospective observational study. Computed tomography (CT) and magnetic resonance imaging (MRI) of the AA joint were compared to a retrospectively reviewed control group. A novel surgical approach consisting of a dorsal internal fixation technique was performed in six dogs. For affected dogs, the mean normalised difference between the dorso-ventral atlas canal and the dorso-ventral axis canal was 29.67% (median of 35.07%, standard deviation 25.64%), while in normal dogs a mean difference of 4.67% (median of 3.95%, standard deviation 5.21%) was observed. On MRI, 12/12 affected dogs had spinal cord compression, which was classified as reducible (3/12), partially reducible (6/12) and non-reducible (3/12). In surgically operated dogs, follow-up CT showed a partial or complete reduction of the previous spinal cord compression with a consistent amelioration or resolution of the presenting complaints. The proposed surgical technique was safe and effective in dogs with partially or completely reducible spinal cord compression.

Frameless stereotactic volumetric modulated arc radiotherapy of brachial plexus tumours in dogs: 10 cases.

OBJECTIVE: Treatment of canine peripheral nerve sheath tumours (PNSTs) is challenging and prognosis after surgical resection is considered poor. The aim of this study was to evaluate the feasibility and effectiveness of stereotactic radiotherapy (RT) of these tumours. METHODS: 10 dogs with clinical symptoms and MRI findings consistent with PNSTs of the brachial plexus, branches and nerve roots were treated with linear accelerator-based volumetric-modulated arc radiotherapy (VMAT) with a dose of 35 Gy/5 fractions. Clinical and MRI follow-up examinations were planned and radiotoxicity and survival times were investigated. RESULTS: Tumours involved the plexus and proximal nerves in three dogs, the plexus, proximal nerves and nerve roots in five dogs and the nerve roots and proximal nerves in two dogs. Partial response and partial or complete reductions of neurological deficits were observed in all the treated dogs. Local recurrence was observed in 9/10 of treated dogs. No symptom directly referable to radiotoxicity was observed. Mean overall survival of 371 ± 30 days [95% confidence interval (CI) of (315-427)] and mean progression-free survival of 240 ± 30 days (95% CI of 188-291) from this work are comparable with surgical literature data regarding the plexus and proximal nerve localization, but are superior in comparison with nerve root localization. CONCLUSION: VMAT can be a safe and viable alternative to surgery in cases of canine brachial plexus PNSTs involving the proximal nerves and nerve roots. Advances in knowledge: To our knowledge, this is the first prospective observational clinical study regarding VMAT stereotactic RT treatment for canine brachial plexus PNSTs and suggests that VMAT may achieve at least similar clinical outcome than surgery in a safer way.

Zygomatic arch-atlas wing stabilization in 5 dogs with atlanto-occipital dislocation.

The aim of this work was to present a novel minimally invasive surgical stabilization technique for canine atlanto-occipital dislocation and to report the associated magnetic resonance imaging (MRI) findings. All 5 dogs in this case series underwent 1.5 T MRI of the head and neck and 3 underwent both MRI and computed tomography (CT). Atlanto-occipital dislocations were diagnosed based on the increased joint space between the occipital condyles and the atlas on MRI. Surgery was performed immediately with a never previously described fixation technique based on an external ligature. The stabilization was performed via 4 holes drilled in the zygomatic processes and in the atlas wings on each side. A nylon monofilament of 1 mm diameter was inserted in the 4 holes, and an O-shaped ligature was carried out externally to the skin through the ipsilateral zygomatic arch. Ligatures were removed within 2 months. At the postsurgical follow-up examination, 14 days after surgery, all dogs were found to be ambulatory. Atlanto-occipital stability was assessed by clinical examination with an average of 24 months of follow-up. The positive outcomes in this case series suggest that atlanto-occipital dislocation may be surgically treated with this novel technique, irrespective of the severity of the clinical presentation and associated lesions observed on MRI.

FEASIBILITY FOR USING HYPOFRACTIONATED STEREOTACTIC VOLUMETRIC MODULATED ARC RADIOTHERAPY (VMAT) WITH ADAPTIVE PLANNING FOR TREATMENT OF THYMOMA IN RABBITS: 15 CASES.

Thymoma is a relatively common tumor in rabbits. Treatment with surgery, radiation therapy, and chemotherapy alone or in combination has been reported with varying outcomes. Stereotactic volumetric modulated arc radiotherapy delivered in a hypofractionated manner allows high doses of radiation to be delivered to the target volume while allowing sparing of adjacent critical structures. This therapy is ideally suited for thymomas in rabbits given their size, the difficulty of multiple anesthesia episodes and the complexity of the radiotherapy plans required due to the tumor's proximity to the heart, lungs, and mediastinal structures. Fifteen rabbits with thymoma were prospectively recruited for this observational, single institution, single arm clinical study. All rabbits were imaged with both computed tomography (CT) and magnetic resonance imaging (MRI). A total dose of 40 Gy in six fractions was delivered using a single arc over an 11-day period with repeat CT simulation done every other fraction for adaptive planning. Follow-up evaluation was done through repeat CT and MRI imaging and revealed complete responses using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Two rabbits had died at 618 and 718 days, 10 were alive and three were lost to follow-up. Observed acute and late effects were graded according to the Veterinary Radiation Therapy Oncology Group (VRTOG) criteria and were found to be minimal.

Hydrated nucleus pulposus extrusion in dogs: correlation of magnetic resonance imaging and microsurgical findings.

BACKGROUND: Magnetic resonance imaging (MRI) patterns of canine cervical hydrated nucleus pulposus extrusion (HNPE) have been described by a few reports, but the correlation between microsurgical and MRI features has never been investigated. The aim of this study was to compare the MRI features of HNPE with microsurgical findings and cytological outcomes and also to investigate the anatomical and pathophysiological aspects of the disease. METHODS: A prospective clinical study was conducted in 36 dogs suffering from HNPE. The diagnosis was based on high-field MRI findings of ventral extradural lesions, adjacent to the dorsal aspect of intervertebral discs, characterised by high signal intensity in T2-weighted sequences and hypointensity in T1-weighted sequences. MRI images were analysed with regard to the intervertebral space involved, the grading of spinal cord compression, the signal intensity and distribution of the material, and the thickness and signal intensity of the involved discs. All patients underwent microsurgical decompression and direct observations were recorded and films of the surgical procedure analysed. RESULTS: The majority of patients had acute onset of clinical signs (78 %), the patient did not exhibit signs of pain in 75 % of dogs and neurological deficits varied from slight tetraparesis (33 %) to tetraplegia (28 %). The localization of the extruded disc material was ventral relative to the dorsal longitudinal ligament that was lifted dorsally and appeared intact at the site of compression. Direct microsurgical observations of the HNPE sites showed that extruded disc material was collected within the fibres of the dorsal longitudinal ligament. The consistency was gelatinous in 42 %, water-like in 33 %, and lumpy liquid in 25 % of cases. Cytological samples did not detect the presence of inflammation, bacteria, fungi, neoplastic cells or foreign material. CONCLUSIONS: Microsurgical features of HNPE suggest that the extruded disc is collected within the fibres of the dorsal longitudinal ligament and this may explain the typical MRI appearance of this disease. Further pathophysiological studies are needed to investigate why the cervical nucleus pulposus extrusion appears to occur without obvious trauma.

Advanced communication infrastructure for pre-hospital EMS care.

The traditional communication infrastructure of the pre-hospital Emergency Medical System (EMS) is limited to voice communication using radio or cell phone technologies. With the emergence of 3rd Generation wireless networks (3G) and enhanced mobile devices capable of data communication (e.g., mobile tablets, PDAs with cell phones, or cell phones with PDA capabilities), the voice communication can be enhanced with interactive data messaging and perhaps even with interactive video communication. However, video requires substantially more bandwidth which 4th Generation (4G) systems are promising. However, their availability is limited. We present an infrastructure that allows dynamic selection of the best data transport mode in the pre-hospital EMS environment.

Expert validation of the knowledge base for E-CAD - a pre-hospital dispatch triage decision support system.

The knowledge base (KB) for E-CAD (Enhanced Computer-Aided Dispatch), a triage decision support system for Emergency Medical Dispatch (EMD) of medical resources in trauma cases, is being evaluated. We aim to achieve expert consensus for validation and refinement of the E-CAD KB using the modified Delphi technique. Evidence-based, expert-validated and refined KB will provide improved EMD practice guidelines and may facilitate acceptance of the E-CAD by state-wide professionals.

Application of speech recognition data entry enhancements in an Electronic Patient Care Report (ePCR).

Based on the Alabama Patient Care Report we developed a basic Electronic Patient Care Report (ePCR) to collect data in an EMS environment. The ePCR GUI is now enhanced using speech recognition to provide speech-based command and control mechanisms to input structured data and initiate processes. This voice-enabled ePCR (vePCR) is used to evaluate the feasibility of handling EMS test cases and to get user feedback about the speech recognition functionality and usefulness.