Juha Korhonen

Serum human chorionic gonadotropin dynamics during spontaneous resolution of ectopic pregnancy

OBJECTIVE To study serum hCG dynamics in patients with ectopic pregnancy (EP) selected for expectant management. DESIGN A prospective observational study. SETTING Helsinki University Central Hospital, Helsinki, Finland. SUBJECTS One hundred eighteen patients, who were selected for expectant management among 493 patients with EP. INTERVENTIONS Patients were examined every 1 to 3 days using transvaginal sonography and serum hCG determinations until hCG values < 10 IU/L (conversion factor to SI unit, 1 IU/L = 2.93 pmol/L) were reached. Laparoscopy was performed if the patient developed abdominal pains or intra-abdominal hemorrhage as revealed by sonography. MAIN OUTCOME MEASURE Serum hCG level. RESULTS The median gestational age at the start of follow-up in patients with a spontaneous resolution was 44 days and in patients requiring laparoscopy was 48 days. The success rate for a spontaneous resolution was 88% when the initial hCG level was < 200 IU/L but only 25% at levels > 2,000 IU/L. In the 77 patients with a spontaneous resolution, the initial median hCG concentration was 374 IU/L (range, 20 to 10,762 IU/L) and it decreased to normal in 4 to 67 days (mean, 20 days). In the 41 patients requiring laparoscopy the median initial hCG concentration was 741 IU/L (range, 165 to 14,047 IU/L); a normal level was reached in 3 to 43 days (mean, 12 days) after operation. Follow-up period before operation was 1 to 24 days (mean, 9 days). Laparoscopy was indicated in two thirds of the patients with a serum hCG level > 64% of the initial value after 7 days of follow-up. CONCLUSIONS Spontaneous resolution of EP correlated with a low and rapidly decreasing hCG level.

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.

Low-dose oral methotrexate with expectant management of ectopic pregnancy

Objective To investigate recovery times and need for laparoscopy in women with ectopic pregnancy who were treated for 5 days 2.5 mg/day of oral methotrexate or placebo. Methods Sixty women with ectopic pregnancy among patients of an outpatient clinic specializing in early pregnancy disorders were selected for medical treatment in a double-blind, placebo-controlled study. The diagnosis was made by transvaginal sonography and serum hCG determinations, either at admission or after repeated examinations. Women were recruited for the study if they had mild symptoms: the hCG increase was less than 50% within 2 days, the diameter of the ectopic pregnancy was less than 40 mm, there were no signs of intra-abdominal bleeding by transvaginal sonography, and there were no secondary reasons for laparoscopy. Either 2.5 mg of methotrexate or placebo was given orally for 5 days. Serum hCG was determined after 2 days, and hCG, red blood cell count, white blood cell count, platelet count, and serum glutamic-oxaloacetic transaminase were measured; transvaginal sonography was performed after 5 and 12 days. Expectant management was continued individually with check-ups at 1–3-week intervals. Laparoscopy was performed if the patient developed abdominal pain or intra-abdominal hemorrhage, as seen by transvaginal sonography. Statistical analysis was by paired or unpaired t test, Mann-Whitney U test, regression analysis, and repeated measures analysis of variance. Results Seventy-seven percent of the patients recovered without the need for laparoscopy in both groups, and there were no significant differences in recovery times or the need for laparoscopy between groups. Conclusion Oral methotrexate, 2.5 mg for 5 days, does not appear to be more effective than placebo in the treatment of ectopic pregnancy in women eligible for expectant management.

Failure of creatine kinase to predict ectopic pregnancy

OBJECTIVE To investigate serum creatine kinase (CK) levels in pregnant women with ectopic pregnancy (EP), spontaneous abortion, and normal pregnancy with comparable serum hCG concentrations. DESIGN A retrospective, case-controlled study. SETTING Helsinki University Central Hospital, Helsinki, Finland. PATIENTS Forty-four patients with a suspicion of EP of which 15 had laparoscopically confirmed tubal pregnancies; 15 had a spontaneous abortion, a blighted ovum, or a missed abortion; and 14 patients a normal intrauterine pregnancy. INTERVENTIONS The diagnosis was made by transvaginal sonography and serum hCG determinations either at admission or after repeated examinations. Ectopic pregnancy was confirmed and treated by laparoscopy. MAIN OUTCOME MEASURES Serum CK and hCG levels. RESULTS No significant differences in CK levels were observed between the groups by one-way analysis of variance and no correlation was found between serum CK and hCG levels within any group. CONCLUSIONS Creatine kinase does not appear to be useful in the diagnosis of early EP.

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.

Emergency cesarean section: the effect of delay on umbilical arterial gas balance and Apgar scores

Background. We wanted to conduct a prospective study on the dynamics of emergency cesarean section (ECS) in terms of fetal survival and morbidity.

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.

Implementation of adaptive radiation therapy for urinary bladder carcinoma: Imaging, planning and image guidance

Abstract Background. Adaptive radiation therapy (ART) for urinary bladder cancer has emerged as a promising alternative to conventional RT with potential to minimize radiation-induced toxicity to healthy tissues. In this work we have studied bladder volume variations and their effect on healthy bladder dose sparing and intrafractional margins, in order to refine our ART strategy. Material and methods. An online ART treatment strategy was followed for five patients with urinary bladder cancer with the tumors demarcated using Lipiodol®. A library of 3–4 predefined treatment plans for each patient was created based on four successive computed tomography (CT) scans. Cone beam CT (CBCT) images were acquired before each treatment fraction and after the treatment at least weekly. In partial bladder treatment the sparing of the healthy part of the bladder was investigated. The bladder wall displacements due to bladder filling were determined in three orthogonal directions (CC, AP, DEX-SIN) using the treatment planning CT scans. An ellipsoidal model was applied in order to find the theoretical maximum values for the bladder wall displacements. Moreover, the actual bladder filling rate during treatment was evaluated using the CBCT images. Results. In partial bladder treatment the volume of the bladder receiving high absorbed doses was generally smaller with a full than empty bladder. The estimation of the bladder volume and the upper limit for the intrafractional movement of the bladder wall could be represented with an ellipsoidal model with a reasonable accuracy. Observed maximum growth of bladder dimensions was less than 10 mm in all three orthogonal directions during 15 minute interval. Conclusion. The use of Lipiodol contrast agent enables partial bladder treatment with reduced irradiation of the healthy bladder volume. The ellipsoidal bladder model can be used for the estimation of the bladder volume changes and the upper limit of the bladder wall movement during the treatment fraction.

Feasibility of MRI-only treatment planning for proton therapy in brain and prostate cancers: Dose calculation accuracy in substitute CT images

PURPOSE Magnetic resonance imaging (MRI) is increasingly used for radiotherapy target delineation, image guidance, and treatment response monitoring. Recent studies have shown that an entire external x-ray radiotherapy treatment planning (RTP) workflow for brain tumor or prostate cancer patients based only on MRI reference images is feasible. This study aims to show that a MRI-only based RTP workflow is also feasible for proton beam therapy plans generated in MRI-based substitute computed tomography (sCT) images of the head and the pelvis. METHODS The sCTs were constructed for ten prostate cancer and ten brain tumor patients primarily by transforming the intensity values of in-phase MR images to Hounsfield units (HUs) with a dual model HU conversion technique to enable heterogeneous tissue representation. HU conversion models for the pelvis were adopted from previous studies, further extended in this study also for head MRI by generating anatomical site-specific conversion models (a new training data set of ten other brain patients). This study also evaluated two other types of simplified sCT: dual bulk density (for bone and water) and homogeneous (water only). For every clinical case, intensity modulated proton therapy (IMPT) plans robustly optimized in standard planning CTs were calculated in sCT for evaluation, and vice versa. Overall dose agreement was evaluated using dose-volume histogram parameters and 3D gamma criteria. RESULTS In heterogeneous sCTs, the mean absolute errors in HUs were 34 (soft tissues: 13, bones: 92) and 42 (soft tissues: 9, bones: 97) in the head and in the pelvis, respectively. The maximum absolute dose differences relative to CT in the brain tumor clinical target volume (CTV) were 1.4% for heterogeneous sCT, 1.8% for dual bulk sCT, and 8.9% for homogenous sCT. The corresponding maximum differences in the prostate CTV were 0.6%, 1.2%, and 3.6%, respectively. The percentages of dose points in the head and pelvis passing 1% and 1 mm gamma index criteria were over 91%, 85%, and 38% with heterogeneous, dual bulk, and homogeneous sCTs, respectively. There were no significant changes to gamma index pass rates for IMPT plans first optimized in CT and then calculated in heterogeneous sCT versus IMPT plans first optimized in heterogeneous sCT and then calculated on standard CT. CONCLUSIONS This study demonstrates that proton therapy dose calculations on heterogeneous sCTs are in good agreement with plans generated with standard planning CT. An MRI-only based RTP workflow is feasible in IMPT for brain tumors and prostate cancers.

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.