Contrast-enhanced, conebeam CT-based, fractionated radiotherapy and follow-up monitoring of orthotopic mouse glioblastoma: a proof-of-concept study.

BACKGROUND: Despite aggressive treatment regimens comprising surgery and radiochemotherapy, glioblastoma (GBM) remains a cancer entity with very poor prognosis. The development of novel, combined modality approaches necessitates adequate preclinical model systems and therapy regimens that closely reflect the clinical situation. So far, image-guided, fractionated radiotherapy of orthotopic GBM models represents a major limitation in this regard. METHODS: GL261 mouse GBM cells were inoculated into the right hemispheres of C57BL/6 mice. Tumor growth was monitored by contrast-enhanced conebeam CT (CBCT) scans. When reaching an average volume of approximately 7 mm3, GBM tumors were irradiated with daily fractions of 2 Gy up to a cumulative dose of 20 Gy in different beam collimation settings. For treatment planning and tumor volume follow-up, contrast-enhanced CBCT scans were performed twice per week. Daily repositioning of animals was achieved by alignment of bony structures in native CBCT scans. When showing neurological symptoms, mice were sacrificed by cardiac perfusion. Brains, livers, and kidneys were processed into histologic sections. Potential toxic effects of contrast agent administration were assessed by measurement of liver enzyme and creatinine serum levels and by histologic examination. RESULTS: Tumors were successfully visualized by contrast-enhanced CBCT scans with a detection limit of approximately 2 mm3, and treatment planning could be performed. For daily repositioning of the animals, alignment of bony structures in native CT scans was well feasible. Fractionated irradiation caused a significant delay in tumor growth translating into significantly prolonged survival in clear dependence of the beam collimation setting and margin size. Brain sections revealed tumors of similar appearance and volume on the day of euthanasia. Importantly, the repeated contrast agent injections were well tolerated, as liver enzyme and creatinine serum levels were only subclinically elevated, and liver and kidney sections displayed normal histomorphology. CONCLUSIONS: Contrast-enhanced, CT-based, fractionated radiation of orthotopic mouse GBM represents a versatile preclinical technique for the development and evaluation of multimodal radiotherapeutic approaches in combination with novel therapeutic agents in order to accelerate translation into clinical testing.

Age-dependent differences in DNA damage after in vitro CT exposure.

PURPOSE: Age dependent radiation sensitivity for DNA damage after in vitro blood exposure by computer tomography (CT) was investigated. MATERIALS AND METHODS: Radiation biomarkers (dicentrics and gammaH2AX) in blood samples of newborns, children under five years and adults after sham exposure (0 mGy), low-dose (41 mGy) and high-dose (978 mGy) in vitro CT exposure were analyzed. RESULTS: Significantly higher levels of dicentric induction were found for the single and combined newborns/children group compared to adults, by a factor of 1.48 (95% CI 1.30-1.68), after exposure to 978 mGy. Although a significant dose response for damage induction and dose-dependent repair was found, the gammaH2AX assay did not show an age-dependent increase in DNA damage in newborns/children compared to adults. This was the case for the gammaH2AX levels after repair time intervals of 30 minutes and 24 hours, after correcting for the underlying background damage. For the low dose of 41 mGy, the power of the dicentric assay was also not sufficient to detect an age-dependent effect in the sample size investigated. CONCLUSION: A 1.5-fold increased level of dicentric aberrations is detected in newborns and children under five years after 1 Gy radiation exposure.

Dose optimization of total or partial skin electron irradiation by thermoluminescent dosimetry.

BACKGROUND: Due to the complex surface of the human body, total or partial skin irradiation using large electron fields is challenging. The aim of the present study was to quantify the magnitude of dose optimization required after the application of standard fields. METHODS: Total skin electron irradiation (TSEI) was applied using the Stanford technique with six dual-fields. Patients presenting with localized lesions were treated with partial skin electron irradiation (PSEI) using large electron fields, which were individually adapted. In order to verify and validate the dose distribution, in vivo dosimetry with thermoluminescent dosimeters (TLD) was performed during the first treatment fraction to detect potential dose heterogeneity and to allow for an individual dose optimization with adjustment of the monitor units (MU). RESULTS: Between 1984 and 2017, a total of 58 patients were treated: 31 patients received TSEI using 12 treatment fields, while 27 patients underwent PSEI and were treated with 4-8 treatment fields. After evaluation of the dosimetric results, an individual dose optimization was necessary in 21 patients. Of these, 7 patients received TSEI (7/31). Monitor units (MU) needed to be corrected by a mean value of 117 MU (±105, range 18-290) uniformly for all 12 treatment fields, corresponding to a mean relative change of 12% of the prescribed MU. In comparison, the other 14 patients received PSEI (14/27) and the mean adjustment of monitor units was 282 MU (±144, range 59-500) to single or multiple fields, corresponding to a mean relative change of 22% of the prescribed MU. A second dose optimization to obtain a satisfying dose at the prescription point was need in 5 patients. CONCLUSIONS: Thermoluminescent dosimetry allows an individual dose optimization in TSEI and PSEI to enable a reliable adjustment of the MUs to obtain the prescription dose. Especially in PSEI in vivo dosimetry is of fundamental importance.

Feasibility of optimized ultralow-dose pulsed fluoroscopy for upper gastrointestinal tract examinations: a phantom study with clinical correlation.

PURPOSE: To establish an optimized ultralow-dose digital pulsed fluoroscopy (FP) protocol for upper gastrointestinal tract examinations and to investigate the radiation dose and image quality. MATERIALS AND METHODS: An Alderson-Rando-Phantom with 60 thermoluminescent dosimeters was used for dose measurements to systematically evaluate the dose-area product (DAP) and organ doses of the optimized FP protocol with the following acquisition parameters: 86.7 kV; 77 mA; 0.9 mm3, automatic image noise and contrast adaption. Subjective image quality, depiction of contrast agent and image noise (5-point Likert scale; 5 = excellent) were assessed in 41 patients, who underwent contrast-enhanced FP with the aforementioned optimized protocol by two radiologists in consensus. A conventional digital radiograph (DR) acquisition protocol served as the reference standard for radiation dose and image quality analyses. RESULTS: Phantom measurements revealed a general dose reduction of approximately 96% per image for the FP protocol as compared to the DR standard. DAP could be reduced by 97%. Significant dose reductions were also found for organ doses, both in the direct and scattered radiation beam with negligible orbital (FP 5.6 × 10-3 vs. DR 0.11; p = 0.02) and gonadal dose exposure (female FP 2.4 × 10-3 vs. DR 0.05; male FP 8 × 10-4 vs. DR 0.03; p ≤ 0.0004). FP provided diagnostic image quality in all patients, although reading scores were significantly lower for all evaluated parameters as compared to the DR standard (p < 0.05). CONCLUSION: Ultralow-dose FP is feasible for clinical routine allowing a significant reduction of direct and scattered dose exposure while providing sufficient diagnostic image quality for reliable diagnosis.

Feasibility of low-dose digital pulsed video-fluoroscopic swallow exams (VFSE): effects on radiation dose and image quality.

Background Fluoroscopy is a frequently used examination in clinical routine without appropriate research evaluation latest hardware and software equipment. Purpose To evaluate the feasibility of low-dose pulsed video-fluoroscopic swallowing exams (pVFSE) to reduce dose exposure in patients with swallowing disorders compared to high-resolution radiograph examinations (hrVFSE) serving as standard of reference. Material and Methods A phantom study (Alderson-Rando Phantom, 60 thermoluminescent dosimeters [TLD]) was performed for dose measurements. Acquisition parameters were as follows: (i) pVFSE: 76.7 kV, 57 mA, 0.9 Cu mm, pulse rate/s 30; (ii) hrVFSE: 68.0 kV, 362 mA, 0.2 Cu mm, pictures 30/s. The dose area product (DAP) indicated by the detector system and the radiation dose derived from the TLD measurements were analyzed. In a patient study, image quality was assessed qualitatively (5-point Likert scale, 5 = hrVFSE; two independent readers) and quantitatively (SNR) in 35 patients who subsequently underwent contrast-enhanced pVFSE and hrVFSE. Results Phantom measurements showed a dose reduction per picture of factor 25 for pVFSE versus hrVFSE images (0.0025 mGy versus 0.062 mGy). The DAP (µGym2) was 28.0 versus 810.5 (pVFSE versus hrVFSE) for an average examination time of 30 s. Direct and scattered organ doses were significantly lower for pVFSE as compared to hrVFSE ( P < 0.05). Image quality was rated 3.9 ± 0.5 for pVFSE versus the hrVFSE standard; depiction of the contrast agent 4.8 ± 0.3; noise 3.6 ± 0.5 ( P < 0.05); SNR calculations revealed a relative decreased of 43.9% for pVFSE as compared to hrVFSE. Conclusion Pulsed VFSE is feasible, providing diagnostic image quality at a significant dose reduction as compared to hrVFSE.

Dose-dependent uptake of 3'-deoxy-3'-[(18) F]fluorothymidine by the bowel after total-body irradiation.

PURPOSE: The aim of this study is to non-invasively assess early, irradiation-induced normal tissue alterations via metabolic imaging with 3'-deoxy-3'-[(18) F]fluorothymidine ([(18) F]FLT). PROCEDURES: Twenty-nine male C57BL/6 mice were investigated by [(18) F]FLT positron emission tomography for 7 days after total body irradiation (1, 4, and 8 Gy) versus 'sham' irradiation (0 Gy). Target/background ratios were determined. The imaging results were validated by histology and immunohistochemistry (Thymidine kinase 1, Ki-67). RESULTS: [(18) F]FLT demonstrated a dose-dependent intestinal accumulation post irradiation. Mean target/background ratio (±standard error) 0 Gy: 1.4 (0.2), 1 Gy: 1.7 (0.1), 4 Gy: 3.1 (0.3), 8 Gy: 4.2 (0.6). Receiver operating characteristic analysis (area under the curve, p value): 0 vs. 1 Gy: 0.81, 0.049; 0 vs. 4 Gy: 1.0, 0.0016; and 0 vs. 8 Gy: 1.0, 0.0020. Immunohistochemistry confirmed the results. CONCLUSIONS: [(18) F]FLT seems to provide dose-dependent information on radiation-induced proliferation in the bowel. This opens the perspective for monitoring therapy-related side-effects as well as assessing, e.g., radiation accident victims.

Radiation exposure and image quality of normal computed tomography brain images acquired with automated and organ-based tube current modulation multiband filtering and iterative reconstruction.

OBJECTIVES: We sought to determine whether radiation dose can be reduced and image quality improved in computed tomography (CT) images of the brain that were acquired with automated exposure control (AEC), organ-based tube current modulation (TCM), multiband filtration (MBF), and iterative reconstruction in image space (IRIS). METHODS: An Alderson-Rando-phantom, equipped with thermoluminescent dosimeters, was used to determine the radiation exposure of organs within the head and neck by different CT brain scan modes. We measured the noise and signal-to-noise ratios and subjectively graded quality criteria in different territories of the brain in spiral CT images of 150 patients. We also derived the radiation exposure from the patient protocols. RESULTS: In the phantom, AEC and TCM reduced the radiation exposure of the lenses, cerebrum, cerebellum, and thyroid gland by 41.9%, 34.5%, 30.5%, and 34.9%, respectively. Brain CT scans from patients investigated with AEC, TCM, MBF, and IRIS were found to have significantly better image quality than with conventional filtered back projection. In addition, the CT dose index and dose-length product were significantly lower with AEC, TCM, MBF, and IRIS by 24.1% and 20.2%, respectively. CONCLUSION: The combination of AEC, TCM, MBF, and IRIS improves image quality while radiation exposure can be reduced, particularly in dose-sensitive organs, such as the lenses and thyroid gland.

Feasibility and radiation dose of high-pitch acquisition protocols in patients undergoing dual-source cardiac CT.

OBJECTIVE: The objective of this study was to compare image quality and radiation dose between high-pitch and established retrospectively and prospectively gated cardiac CT protocols using an Alderson-Rando phantom and a set of patients. MATERIALS AND METHODS: An anthropomorphic Alderson-Rando phantom equipped with thermoluminiscent detectors and a set of clinical patients underwent the following cardiac CT protocols: high-pitch acquisition (pitch 3.4), prospectively triggered acquisition, and retrospectively gated acquisition (pitch 0.2). For patients with sinus rhythm below 65 beats per minute (bpm), high-pitch protocol was used, whereas for patients in sinus rhythm between 65 and 100 bpm, prospective triggering was used. Patients with irregular heart rates or heart rates of ≥ 100 bpm, were examined using retrospectively gated acquisition. Evaluability of coronary artery segments was determined, and effective radiation dose was derived from the phantom study. RESULTS: In the phantom study, the effective radiation dose as determined with thermoluminescent detector (TLD) measurements was lowest in the high-pitch acquisition (1.21, 3.12, and 11.81 mSv, for the high-pitch, the prospectively triggered, and the retrospectively gated acquisition, respectively). There was a significant difference with respect to the percentage of motion-free coronary artery segments (99%, 87%, and 92% for high-pitch, prospectively triggered, and retrospectively gated, respectively (p < 0.001), whereas image noise was lowest for the high-pitch protocol (p < 0.05). CONCLUSION: High-pitch scans have the potential to reduce radiation dose up to 61.2% and 89.8% compared with prospectively triggered and retrospectively gated scans. High-pitch protocols lead to excellent image quality when used in patients with stable heart rates below 65 bpm.

Dual energy CT of the chest: how about the dose?

OBJECTIVE: New generation Dual Source computed tomography (CT) scanners offer different x-ray spectra for Dual Energy imaging. Yet, an objective, manufacturer independent verification of the dose required for the different spectral combinations is lacking. The aim of this study was to assess dose and image noise of 2 different Dual Energy CT settings with reference to a standard chest scan and to compare image noise and contrast to noise ratios (CNR). Also, exact effective dose length products (E/DLP) conversion factors were to be established based on the objectively measured dose. MATERIALS AND METHODS: An anthropomorphic Alderson phantom was assembled with thermoluminescent detectors (TLD) and its chest was scanned on a Dual Source CT (Siemens Somatom Definition) in dual energy mode at 140 and 80 kVp with 14 x 1.2 mm collimation. The same was performed on another Dual Source CT (Siemens Somatom Definition Flash) at 140 kVp with 0.8 mm tin filter (Sn) and 100 kVp at 128 x 0.6 mm collimation. Reference scans were obtained at 120 kVp with 64 x 0.6 mm collimation at equivalent CT dose index of 5.4 mGy*cm. Syringes filled with water and 17.5 mg iodine/mL were scanned with the same settings. Dose was calculated from the TLD measurements and the dose length products of the scanner. Image noise was measured in the phantom scans and CNR and spectral contrast were determined in the iodine and water samples. E/DLP conversion factors were calculated as ratio between the measured dose form the TLDs and the dose length product given in the patient protocol. RESULTS: The effective dose measured with TLDs was 2.61, 2.69, and 2.70 mSv, respectively, for the 140/80 kVp, the 140 Sn/100 kVp, and the standard 120 kVp scans. Image noise measured in the average images of the phantom scans was 11.0, 10.7, and 9.9 HU (P > 0.05). The CNR of iodine with optimized image blending was 33.4 at 140/80 kVp, 30.7 at 140Sn/100 kVp and 14.6 at 120 kVp. E/DLP conversion factors were 0.0161 mSv/mGy*cm for the 140/80 kVp protocol, 0.0181 mSv/mGy*cm for the Sn140/100 kVp mode and 0.0180 mSv/mGy*cm for the 120 kVp examination. CONCLUSION: Dual Energy CT is feasible without additional dose. There is no significant difference in image noise, while CNR can be doubled with optimized dual energy CT reconstructions. A restriction in collimation is required for dose-neutrality at 140/80 kVp, whereas this is not necessary at 140 Sn/100 kVp. Thus, CT can be performed routinely in Dual Energy mode without additional dose or compromises in image quality.

Saving dose in triple-rule-out computed tomography examination using a high-pitch dual spiral technique.

OBJECTIVE: High radiation doses remain a drawback of current triple-rule-out computed tomography (CT) protocols. With dual source CT, a new high-pitch dual spiral technique offers the possibility to acquire an Electrocardiography (ECG)-gated-synchronized dataset of the whole chest in less than 1 second. The aim of this study was to compare the dose of such a protocol to a standard, nongated chest scan and to a conventional, retrospectively ECG-gated triple-rule-out protocol. Also, the efficacy and dose of this dual spiral protocol was to be compared in patients examined with this high-pitch technique and matched controls scanned with the conventional technique. MATERIALS AND METHODS: An anthropomorphic Alderson Rando phantom was equipped with thermoluminescent detectors and scanned with the high-pitch protocol (Siemens Somatom Definition Flash; 2 x 120 kVp, 426 mAseff, 128 x 0.6 mm collimation, pitch 3.2), the nongated chest scan (same scanner; 120 kVp, 160 mAseff, 128 x 0.6 mm, pitch 1.2; equivalent Computed Tomography Dose Index (CTDI) of 7.12 mGy), and the conventional gating technique (Siemens Somatom Definition; 120 kVp, 560 mAseff with ECG pulsing interval at 30%-70% of the R-R cycle, 64 x 0.6 mm, pitch 0.3). Noise was measured in air, central and peripheral soft tissue of the phantom. Conversion factors were determined based on the measured dose and the dose-length products of the scanner. The protocol was then applied with ethics committee approval in 31 patients suffering from acute chest pain. The 120 mL of contrast material (Ultravist 370, Bayer Schering Pharma) was applied at 5 mL/s. Dose was calculated based on the dose-length products and the conversion factor. Image quality was assessed by 2 readers for aorta, pulmonary arteries, and coronary arteries. The results were compared with matched controls scanned with the conventional ECG gating technique and non-ECG gated thorax scans. RESULTS: The dose determined with thermoluminescent dosimeters measurements amounted to 2.65, 2.68, and 19.27 mSv, respectively, for the dual spiral technique, the standard chest scan, and the conventional retrospective technique. There was no significant difference in image noise. Respective conversion factors were 0.0186, 0.0188, and 0.0180 mSv/mGy x cm. In the patient examinations, dose was 4.08 +/- 0.81 mSv with the high-pitch protocol compared with 20.4 +/- 5.3 mSv in the matched controls with the conventional technique, and 4.40 +/- 0.83 mSv for the non-ECG gated thorax scan. Scan times were 0.7 +/- 0.1 seconds for the high-pitch scan and 15 +/- 3 seconds for the conventional chest pain scan. Aorta and pulmonary arteries were depicted in diagnostic quality in both groups. About 84.7% of coronary artery segments were rated as diagnostic in the high-pitch exams (95.4% below 65 bpm and only 72.8% in higher heart rates), whereas 92.9% were diagnostic with the conventional approach. CONCLUSION: The high-pitch dual spiral technique requires only about one-fifth of the dose of conventional ECG gated triple-rule-out protocols, thus matching that of a standard nongated chest scan. With less than 1 second, the scan time is very short. This protocol can be recommended for patients with unclear chest pain with rhythmic heart rates below 65 bpm.