Mika Kapanen

A dual model HU conversion from MRI intensity values within and outside of bone segment for MRI‐based radiotherapy treatment planning of prostate cancer

PURPOSE The lack of electron density information in magnetic resonance images (MRI) poses a major challenge for MRI-based radiotherapy treatment planning (RTP). In this study the authors convert MRI intensity values into Hounsfield units (HUs) in the male pelvis and thus enable accurate MRI-based RTP for prostate cancer patients with varying tissue anatomy and body fat contents. METHODS T1/T2*-weighted MRI intensity values and standard computed tomography (CT) image HUs in the male pelvis were analyzed using image data of 10 prostate cancer patients. The collected data were utilized to generate a dual model HU conversion technique from MRI intensity values of the single image set separately within and outside of contoured pelvic bones. Within the bone segment local MRI intensity values were converted to HUs by applying a second-order polynomial model. This model was tuned for each patient by two patient-specific adjustments: MR signal normalization to correct shifts in absolute intensity level and application of a cutoff value to accurately represent low density bony tissue HUs. For soft tissues, such as fat and muscle, located outside of the bone contours, a threshold-based segmentation method without requirements for any patient-specific adjustments was introduced to convert MRI intensity values into HUs. The dual model HU conversion technique was implemented by constructing pseudo-CT images for 10 other prostate cancer patients. The feasibility of these images for RTP was evaluated by comparing HUs in the generated pseudo-CT images with those in standard CT images, and by determining deviations in MRI-based dose distributions compared to those in CT images with 7-field intensity modulated radiation therapy (IMRT) with the anisotropic analytical algorithm and 360° volumetric-modulated arc therapy (VMAT) with the Voxel Monte Carlo algorithm. RESULTS The average HU differences between the constructed pseudo-CT images and standard CT images of each test patient ranged from -2 to 5 HUs and from 22 to 78 HUs in soft and bony tissues, respectively. The average local absolute value differences were 11 HUs in soft tissues and 99 HUs in bones. The planning target volume doses (volumes 95%, 50%, 5%) in the pseudo-CT images were within 0.8% compared to those in CT images in all of the 20 treatment plans. The average deviation was 0.3%. With all the test patients over 94% (IMRT) and 92% (VMAT) of dose points within body (lower than 10% of maximum dose suppressed) passed the 1 mm and 1% 2D gamma index criterion. The statistical tests (t- and F-tests) showed significantly improved (p ≤ 0.05) HU and dose calculation accuracies with the soft tissue conversion method instead of homogeneous representation of these tissues in MRI-based RTP images. CONCLUSIONS This study indicates that it is possible to construct high quality pseudo-CT images by converting the intensity values of a single MRI series into HUs in the male pelvis, and to use these images for accurate MRI-based prostate RTP dose calculations.

T1/T2*-weighted MRI provides clinically relevant pseudo-CT density data for the pelvic bones in MRI-only based radiotherapy treatment planning.

Abstract Background and purpose. In radiotherapy (RT), target soft tissues are best defined on MR images. In several cases, CT imaging is needed only for dose calculation and generation of digitally reconstructed radiographs (DRRs). Image co-registration errors between MRI and CT can be avoided by using MRI-only based treatment planning, especially in the pelvis. Since electron density information can not be directly derived from the MRI, a method is needed to convert MRI data into CT like data. We investigated whether there is a relationship between MRI intensity and Hounsfield unit (HU) values for the pelvic bones. The aim was to generate a method to convert bone MRI intensity into HU data surrogate for RT treatment planning. Material and methods. The HU conversion model was generated for 10 randomly chosen prostate cancer patients and independent validation was performed in another 10 patients. Data consisted of 800 image voxels chosen within the pelvic bones in both T1/T2*-weighted gradient echo and CT images. Relation between MRI intensity and electron density was derived from calibrated HU-values. The proposed method was tested by constructing five “pseudo”-CT series. Results. We found that the MRI intensity is related to the HU value within a HU range from 0 to 1400 within the pelvic bones. The mean prediction error of the conversion model was 135 HU. Dose calculation based on the pseudo-CT images was accurate and the generated DRRs were of good quality. Conclusions. The proposed method enables generation of clinically relevant pseudo-CT data for the pelvic bones from one MRI series. It is simpler than previously reported approaches which require either acquisition of several MRI series or T2* maps with special imaging sequences. The method can be applied with commercial clinical image processing software. The application requires segmentation of the bones in the MR images.

Commissioning of MRI‐only based treatment planning procedure for external beam radiotherapy of prostate

In radiotherapy, target tissues are defined best on MR images due to their superior soft tissue contrast. Computed tomography imaging is geometrically accurate and it is needed for dose calculation and generation of reference images for treatment localization. Co‐registration errors between MR and computed tomography images can be eliminated using magnetic resonance imaging‐only based treatment planning. Use of ionizing radiation can be avoided which is especially important in adaptive treatments requiring several re‐scans. We commissioned magnetic resonance imaging‐only based procedure for external radiotherapy, treatment planning of the prostate cancer. Geometrical issues relevant in radiotherapy, were investigated including quality assurance testing of the scanner, evaluation of the displacement of skin contour and radiosensitive rectum wall, and detection of intraprostatic fiducial gold seed markers used for treatment localization. Quantitative analysis was carried out for 30 randomly chosen patients. Systematic geometrical errors were within 2.2 mm. The gold seed markers were correctly identified for 29 out of the 30 patients. Positions of the seed midpoints were consistent within 1.3 mm in magnetic resonance imaging and computed tomography. Positional error of rectal anterior wall due to susceptibility effect was minimal. Geometrical accuracy of the investigated equipment and procedure was sufficient for magnetic resonance imaging‐only based radiotherapy, treatment planning of the prostate cancer including treatment virtual simulation. Magn Reson Med, 2013.

Mre11 inhibition by oncolytic adenovirus associates with autophagy and underlies synergy with ionizing radiation

New treatment approaches are needed for hormone refractory prostate cancer. Oncolytic adenoviruses are promising anti‐cancer agents, and their efficacy can be improved by combining with conventional therapies such as ionizing radiation. The aim of this study was to determine the timing of oncolytic adenovirus treatment with regard to radiation and study the mechanisms of synergy in combination treatment. Prostate cancer cells were infected with oncolytic adenoviruses, irradiated and synergy mechanisms were assessed. In vivo models of combination treatment were tested. Radiation and oncolytic viruses were synergistic when viral infection was scheduled 24 hr after irradiation. Combination of oncolytic adenovirus with radiotherapy significantly increased antitumor efficacy in vivo compared to either agent alone. Microarray analysis showed dysregulated pathways including cell cycle, mTOR and antigen processing pathways. Functional analysis showed that adenoviral infection was accompanied with degradation of proteins involved in DNA break repair. Mre11 was degraded for subsequent inactivation of Chk2‐Thr68 in combination treated cells, while γH2AX‐Ser139 was elevated implicating the persistence of DNA double strand breaks. Increased autophagocytosis was seen in combination treated cells. Combination treatment did not increase apoptosis or virus replication. The results provide evidence of the antitumor efficacy of combining oncolytic adenoviruses with irradiation as a therapeutic strategy for the treatment of prostate cancer. Further, these findings propose a molecular mechanism that may be important in radiation induced cell death, autophagy and viral cytopathic effect.

The accuracy of Acuros XB algorithm for radiation beams traversing a metallic hip implant — comparison with measurements and Monte Carlo calculations

In this study, the clinical benefit of the improved accuracy of the Acuros XB (AXB) algorithm, implemented in a commercial radiotherapy treatment planning system (TPS), Varian Eclipse, was demonstrated with beams traversing a high‐Z material. This is also the first study assessing the accuracy of the AXB algorithm applying volumetric modulated arc therapy (VMAT) technique compared to full Monte Carlo (MC) simulations. In the first phase the AXB algorithm was benchmarked against point dosimetry, film dosimetry, and full MC calculation in a water‐filled anthropometric phantom with a unilateral hip implant. Also the validity of the full MC calculation used as reference method was demonstrated. The dose calculations were performed both in original computed tomography (CT) dataset, which included artifacts, and in corrected CT dataset, where constant Hounsfield unit (HU) value assignment for all the materials was made. In the second phase, a clinical treatment plan was prepared for a prostate cancer patient with a unilateral hip implant. The plan applied a hybrid VMAT technique that included partial arcs that avoided passing through the implant and static beams traversing the implant. Ultimately, the AXB‐calculated dose distribution was compared to the recalculation by the full MC simulation to assess the accuracy of the AXB algorithm in clinical setting. A recalculation with the anisotropic analytical algorithm (AAA) was also performed to quantify the benefit of the improved dose calculation accuracy of type ‘c’ algorithm (AXB) over type ‘b’ algorithm (AAA). The agreement between the AXB algorithm and the full MC model was very good inside and in the vicinity of the implant and elsewhere, which verifies the accuracy of the AXB algorithm for patient plans with beams traversing through high‐Z material, whereas the AAA produced larger discrepancies. PACS numbers: 87.55.‐x, 87.55.D‐, 87.55.K‐, 87.55.kd, 87.55.Qr

Feasibility of MRI-based reference images for image-guided radiotherapy of the pelvis with either cone-beam computed tomography or planar localization images

Abstract Purpose. This study introduces methods to conduct image-guided radiotherapy (IGRT) of the pelvis with either cone-beam computed tomography (CBCT) or planar localization images by relying solely on magnetic resonance imaging (MRI)-based reference images. Material and methods. Feasibility of MRI-based reference images for IGRT was evaluated against kV CBCT (50 scans, 5 prostate cancer patients) and kV & MV planar (5 & 5 image pairs and patients) localization images by comparing the achieved patient position corrections to those obtained by standard CT-based reference images. T1/T2*-weighted in-phase MRI, Hounsfield unit conversion-based heterogeneous pseudo-CT, and bulk pseudo-CT images were applied for reference against localization CBCTs, and patient position corrections were obtained by automatic image registration. IGRT with planar localization images was performed manually by 10 observers using reference digitally reconstructed radiographs (DRRs) reconstructed from the pseudo-CTs and standard CTs. Quality of pseudo-DRRs against CT-DRRs was evaluated with image similarity metrics. Results. The SDs of differences between CBCT-to-MRI and CBCT-to-CT automatic gray-value registrations were ≤ 1.0 mm & ≤ 0.8° and ≤ 2.5 mm & ≤ 3.6° with 10 cm diameter cubic VOI and prostate-shaped VOI, respectively. The corresponding values for reference heterogeneous pseudo-CT were ≤ 1.0 mm & ≤ 0.7° and ≤ 2.2 mm & ≤ 3.3°, respectively. Heterogeneous pseudo-CT was the only type of MRI-based reference image working reliably with automatic bone registration (SDs were ≤ 0.9 mm & ≤ 0.7°). The differences include possible residual errors from planning CT to MRI registration. The image similarity metrics were significantly (p ≤ 0.01) better in agreement between heterogeneous pseudo-DRRs and CT-DRRs than between bulk pseudo-DRRs and CT-DRRs. The SDs of differences in manual registrations (3D) with planar kV and MV localization images were ≤ 1.0 mm and ≤ 1.7 mm, respectively, between heterogeneous pseudo-DRRs and CT-DRRs, and ≤ 1.4 mm and ≤ 2.1 mm between bulk pseudo-DRRs and CT-DRRs. Conclusion. This study demonstrated that it is feasible to conduct IGRT of the pelvis with MRI-based reference images.

Absorbed doses behind bones with MR image‐based dose calculations for radiotherapy treatment planning

PURPOSE Magnetic resonance (MR) images are used increasingly in external radiotherapy target delineation because of their superior soft tissue contrast compared to computed tomography (CT) images. Nevertheless, radiotherapy treatment planning has traditionally been based on the use of CT images, due to the restrictive features of MR images such as lack of electron density information. This research aimed to measure absorbed radiation doses in material behind different bone parts, and to evaluate dose calculation errors in two pseudo-CT images; first, by assuming a single electron density value for the bones, and second, by converting the electron density values inside bones from T(1)∕T(2)∗-weighted MR image intensity values. METHODS A dedicated phantom was constructed using fresh deer bones and gelatine. The effect of different bone parts to the absorbed dose behind them was investigated with a single open field at 6 and 15 MV, and measuring clinically detectable dose deviations by an ionization chamber matrix. Dose calculation deviations in a conversion-based pseudo-CT image and in a bulk density pseudo-CT image, where the relative electron density to water for the bones was set as 1.3, were quantified by comparing the calculation results with those obtained in a standard CT image by superposition and Monte Carlo algorithms. RESULTS The calculations revealed that the applied bulk density pseudo-CT image causes deviations up to 2.7% (6 MV) and 2.0% (15 MV) to the dose behind the examined bones. The corresponding values in the conversion-based pseudo-CT image were 1.3% (6 MV) and 1.0% (15 MV). The examinations illustrated that the representation of the heterogeneous femoral bone (cortex denser compared to core) by using a bulk density for the whole bone causes dose deviations up to 2% both behind the bone edge and the middle part of the bone (diameter <2.5 cm), but in the opposite directions. The measured doses and the calculated ones in the standard CT image were within 0.4% (through gelatine only) and 0.9% (behind bones). CONCLUSIONS This study indicates that the decrease in absorbed dose is not dependent on the bone diameter with all types of bones. Thus, performing dose calculation in a pseudo-CT image by assuming a single electron density value for the bones can lead to a substantial misrepresentation of the dose distribution profile. This work showed that dose calculation accuracy can be improved by using a pseudo-CT image in which the electron density values have been converted from the MR image intensity values inside bones.

Influence of MRI-based bone outline definition errors on external radiotherapy dose calculation accuracy in heterogeneous pseudo-CT images of prostate cancer patients

Abstract Background. This work evaluates influences of susceptibility-induced bone outline shift and perturbations, and bone segmentation errors on external radiotherapy dose calculation accuracy in magnetic resonance imaging (MRI)-based pseudo-computed tomography (CT) images of the male pelvis. Material and methods. T1/T2*-weighted fast gradient echo, T1-weighted spin echo and T2-weighted fast spin echo images were used in bone detection investigation. Bone edge location and bone diameter in MRI were evaluated by comparing those in the images with actual physical measurements of fresh deer bones positioned in a gelatine phantom. Dose calculation accuracy in pseudo-CT images was investigated for 15 prostate cancer patients. Bone outlines in T1/T2*-weighted images were contoured and additional segmentation errors were simulated by expanding and contracting the bone contours with 1 mm spacing. Heterogeneous pseudo-CT images were constructed by adopting a technique transforming the MRI intensity values into Hounsfield units with separate conversion models within and outside of bone segment. Results. Bone edges and diameter in the phantom were illustrated correctly within a 1 mm-pixel size in MRI. Each 1 mm-sized systematic error in bone segment resulted in roughly 0.4% change to the prostate dose level in the pseudo-CT images. The prostate average (range) dose levels in pseudo-CT images with additional systematic bone segmentation errors of −2 mm, 0 mm and 2 mm were 0.5% (−0.5–1.4%), −0.2% (−1.0–0.7%), and −0.9% (−1.8–0.0%) compared to those in CT images, respectively, in volumetric modulated arc therapy treatment plans calculated by Monte Carlo algorithm. Conclusions. Susceptibility-induced bone outline shift and perturbations do not result in substantial uncertainty for MRI-based dose calculation. Dose consistency of 2% can be achieved reliably for the prostate if heterogeneous pseudo-CT images are constructed with ≤± 2 mm systematic error in bone segment.

Patterns of relapse following definitive treatment of head and neck squamous cell cancer by intensity modulated radiotherapy and weekly cisplatin

Eighty-three patients with oropharyngeal, hypopharyngeal or laryngeal cancer were treated with concomitant cisplatin 40 mg/m(2) once a week during the radiotherapy and IMRT up to a total dose of 70 Gy. The 2-year rate of local control, overall survival and disease specific survival were 84%, 82% and 89%, respectively. The corresponding 5-year Kaplan-Meier estimates were 79%, 69% and 76%.

Submandibular gland-sparing intensity modulated radiotherapy in the treatment of head and neck cancer: Sites of locoregional relapse and survival

Abstract Background and purpose. To evaluate the patterns of locoregional relapse and survival following submandibular gland (SMG)-sparing intensity modulated radiotherapy (IMRT). Patients and methods. Eighty patients with laryngeal (n = 15), oropharyngeal (n = 50), hypopharyngeal (n = 11) or nasopharyngeal cancer (n = 4) were treated by submandibular gland-sparing IMRT for head and neck squamous cell cancer between July 2000 and December 2008. All patients were treated by bilateral IMRT. Thirty-nine (49%) received definitive radiotherapy (RT) and 41 (51%) postoperative RT. The contralateral parotid gland (PG) and SMG were included in the dose optimization planning program with intent to keep the mean doses for PG and SMG below 23 Gy and 28–30 Gy, respectively. The ipsilateral glands were also spared when considered feasible. Results. During a median follow-up time of 51 months (range, 24–117 months) nine local recurrent tumors were observed. Four of these nine patients were salvaged by surgery with no further recurrence. All local recurrences were located within the high-dose CTVs. None of the locally recurrent cancers were located at the vicinity of the spared PGs or SMGs. No recurrent tumors were observed in the contralateral neck. The Kaplan-Meier estimate for local control at five years following IMRT was 88% for the whole cohort and the corresponding figure for local control following salvage surgery was 94%. The estimates for five-year overall survival and disease-specific survival were 85% and 90%, respectively. Conclusion. In selected head and neck cancer patients who are estimated to have a low risk of cancer recurrence at the nodal levels I–II and who are treated with SMG-sparing IMRT the risk of cancer recurrence at the vicinity of the spared salivary glands is low.