Evaluation of MRI-only based online adaptive radiotherapy of abdominal region on MR-linac

Purpose A hybrid magnetic resonance linear accelerator (MRL) can perform magnetic resonance imaging (MRI) with high soft-tissue contrast to be used for online adaptive radiotherapy (oART). To obtain electron densities needed for the oART dose calculation, a computed tomography (CT) is often deformably registered to MRI. Our aim was to evaluate an MRI-only based synthetic CT (sCT) generation as an alternative to the deformed CT (dCT)-based oART in the abdominal region. Methods The study data consisted of 57 patients who were treated on a 0.35 T MRL system mainly for abdominal tumors. Simulation MRI-CT pairs of 43 patients were used for training and validation of a prototype convolutional neural network sCT-generation algorithm, based on HighRes3DNet, for the abdominal region. For remaining test patients, sCT images were produced from simulation MRIs and daily MRIs. The dCT-based plans were re-calculated on sCT with identical calculation parameters. The sCT and dCT were compared in terms of geometric agreement and calculated dose. Results The mean and one standard deviation of the geometric agreement metrics over dCT-sCT-pairs were: mean error of 8 +/- 10 HU, mean absolute error of 49 +/- 10 HU, and Dice similarity coefficient of 55 +/- 12%, 60 +/- 5%, and 82 +/- 15% for bone, fat, and lung tissues, respectively. The dose differences between the sCT and dCT-based dose for planning target volumes were 0.5 +/- 0.9%, 0.6 +/- 0.8%, and 0.5 +/- 0.8% at D-2%, D-50%, and D-98% in physical dose and 0.8 +/- 1.4%, 0.8 +/- 1.2%, and 0.6 +/- 1.1% in biologically effective dose (BED). For organs-at-risk, the dose differences of all evaluated dose-volume histogram points were within [-4.5%, 7.8%] and [-1.1 Gy, 3.5 Gy] in both physical dose and BED. Conclusions The geometric agreement metrics were within typically reported values and most average relative dose differences were within 1%. Thus, an MRI-only sCT-based approach is a promising alternative to the current clinical practice of the abdominal oART on MRL.Peer reviewe

Three-dimensional T1 quantification techniques for assessment of cartilage quality using dGEMRIC

Osteoarthritis (OA) is a common chronic disease and one of the major global causes for functional disabilities. The disease is characterized by loss and degradation of cartilage, commonly affecting the knees and hips. Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) is a previously presented method for identification of early OA using magnetic resonance imaging (MRI). By quantifying the T1 parameter in the cartilage after distribution of a contrast agent, a measure of the glycosaminoglycan (GAG) content is retrieved, which in turn is known to be decreased at early stages of OA. In this thesis a series of three-dimensional (3D) T1 quantification methods have been developed and evaluated for use in dGEMRIC. Traditionally, such sequences have not been widely adopted for this purpose and in this work it has been shown that the main obstacles are related to B1 variations within the volume. As part of the work a 3D Look-Locker (3D-LL) T1 quantification pulse sequence have been created. In addition, new methods were developed for correction of B1 inhomogeneities and slab profile flip angle variations in the 3D-LL data. From in vivo and phantom measurements the methods were shown to be reliable, with T1 results that agreed very well to gold standard two-dimensional inversion recovery (2D-IR). A 3D variable flip angle (3D-VFA) T1 quantification sequence in combination with a B1 mapping sequence was also investigated. The results with and without B1 correction was studied in vivo and in phantoms. It was concluded that 3D-VFA should always be used with B1 correction, especially at higher field strengths In addition, two dedicated clinical studies were set up, to both verify the usability of the developed methods and to explore new dGEMRIC applications. In one of these studies, the repeatability of successive dGEMRIC measurements for each of the T1 quantification methods was investigated for a group of subjects at risk of developing OA. 2D-IR and 3D-LL performed equally well, while 3D-VFA (without B1 correction) was inferior. Repeatability was shown to be similar to previously reported results in healthy subjects. The other of these studies was a time-response study, using 3D-LL, to explore the feasibility of performing dGEMRIC in the meniscus. It was concluded that the temporal contrast uptake in the meniscus follows that of the articular cartilage and that differences can be seen between vascular and avascular parts of the meniscus. The overall conclusion of this work is that 3D T1 quantification in dGEMRIC is feasible and should allow for both new and improved means of diagnostics

Local Flip Angle Correction for Improved Volume T1-Quantification in Three-Dimensional dGEMRIC Using the Look-Locker Technique

Purpose: To present an evaluation method for three-dimensional Look-Locker (3D-LL) based T1 quantification, calculating correct T1 values independent of local flip angle (FA) variations. The method was evaluated both in phantoms and in vivo in a delayed Gadolinium Enhanced MRI of Cartilage (dGEMRIC) study with 33 subjects. Materials and Methods: T1 was measured with 3D-LL, using both local FA correction and a precalculated FA slice profile. and compared with standard constant FA correction, for all slices in phantoms and in both femur condyles in vivo. T1 measured using two-dimensional Inversion Recovery (2D-IR) was used as gold standard. Results: Due to the FA being slice dependent, the standard constant FA correction results in erroneous T1 (systematic error = 109.1 ms in vivo), especially in the outer slices. With local FA correction. the calculated T1 is excellent for all slices in phantoms (<5% deviation from 2D-IR). In vivo the performance is lower (systematic error = -57.5ms), probably due to imperfect inversion. With precalculated FA correction the performance is very good also in vivo (systematic error = 13.3 ms). Conclusion: With the precalculated FA correction method, the 3D-LL sequence is robust enough for in vivo dGEMRIC, even outside the centermost slices

Residual hip dysplasia at 1 year after treatment for neonatal hip instability is not related to degenerative joint disease in young adulthood: a 21-year follow-up study including dGEMRIC.

Developmental dysplasia of the hip (DDH) is associated with an increased risk of early hip osteoarthritis (OA). We aimed to examine the outcome at the completion of growth in a cohort of children who had residual acetabular dysplasia at age 1 year following early treatment for neonatal instability of the hip (NIH)

Unthreaded Fixation of Slipped Capital Femoral Epiphysis Leads to Continued Growth of the Femoral Neck.

The optimal treatment for slipped capital femoral epiphysis (SCFE) remains controversial. In Sweden, the standard treatment is unthreaded fixation over the physis, with the purpose to permit continued growth of the femoral neck. The aim of the present study was to verify and quantify longitudinal growth of the femoral neck after in situ pinning with the Hansson hook-pin

In vivo transport of Gd-DTPA(2-) into human meniscus and cartilage assessed with delayed gadolinium-enhanced MRI of cartilage (dGEMRIC)

Background: Impaired stability is a risk factor in knee osteoarthritis (OA), where the whole joint and not only the joint cartilage is affected. The meniscus provides joint stability and is involved in the early pathological progress of OA. Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) has been used to identify pre-radiographic changes in the cartilage in OA, but has been used less commonly to examine the meniscus, and then using only a double dose of the contrast agent. The purpose of this study was to enable improved early OA diagnosis by investigate the temporal contrast agent distribution in the meniscus and femoral cartilage simultaneously, in healthy volunteers, using 3D dGEMRIC at two different doses of the contrast agent Gd-DTPA(2-). Methods: The right knee in 12 asymptomatic volunteers was examined using a 3D Look-Locker sequence on two occasions after an intravenous injection of a double or triple dose of Gd-DTPA(2-) (0.2 or 0.3 mmol/kg body weight). The relaxation time (T-1) and relaxation rate (R-1 = 1/T-1) were measured in the meniscus and femoral cartilage before, and 60, 90, 120 and 180 minutes after injection, and the change in relaxation rate (Delta R-1) was calculated. Paired t-test and Analysis of Variance (ANOVA) were used for statistical evaluation. Results: The triple dose yielded higher concentrations of Gd-DTPA(2-) in the meniscus and cartilage than the double dose, but provided no additional information. The observed patterns of Delta R-1 were similar for double and triple doses of the contrast agent. Delta R-1 was higher in the meniscus than in femoral cartilage in the corresponding compartments at all time points after injection. Delta R-1 increased until 90-180 minutes in both the cartilage and the meniscus (p < 0.05), and was lower in the medial than in the lateral meniscus at all time points (p < 0.05). A faster increase in Delta R-1 was observed in the vascularized peripheral region of the posterior medial meniscus, than in the avascular central part of the posterior medial meniscus during the first 60 minutes (p < 0.05). Conclusion: It is feasible to examine undamaged meniscus and cartilage simultaneously using dGEMRIC, preferably 90 minutes after the injection of a double dose of Gd-DTPA(2-) (0.2 mmol/kg body weight)

Delayed gadolinium-enhanced MRI of meniscus (dGEMRIM) and cartilage (dGEMRIC) in healthy knees and in knees with different stages of meniscus pathology

Background: Lesions in the meniscus are risk factors for developing knee osteoarthritis (OA), not least because of the role of the meniscus in the pathological progression of OA. Delayed gadolinium enhanced MRI of cartilage (dGEMRIC) has extensively been used to identify pre-radiographic cartilage changes in OA. In contrast, its counterpart with regard to examination of the meniscus, gadolinium enhanced MRI of meniscus (dGEMRIM), has been less utilized. In this study we use 3D dGEMRIM in patients with meniscus lesions and compare them with previous results of healthy individuals. Methods: Eighteen subjects with MRI-verified posteromedial meniscus lesions and 12 healthy subjects with non-injured and non-symptomatic knee joints, together 30 volunteers, were examined using 3D Look-Locker sequence after intravenous injection of Gd-DTPA2- (0.2 mmol/kg body weight). Relaxation time (T1) was measured in the posterior meniscus and femoral cartilage before and 60, 90, 120 and 180 min after injection. Relaxation rate (R1 = 1/T1) and change in relaxation rate (ΔR1) were calculated. For statistical analyses, Student's t-test and Analysis of Variance (ANOVA) were used. Results: The pre-contrast diagnostic MRI identified two sub-cohorts in the 18 patients with regard to meniscus injury: 1) 11 subjects with MRI verified pathological intrameniscal changes (grade 2) in the posteromedial meniscus only and no obvious cartilage changes. The lateral meniscus showed no pathology. 2) 7 subjects with MRI verified pathological rupture (grade 3) of the posteromedial meniscus and pathological changes in the lateral meniscus and/or medial and lateral joint cartilage. Comparisons of pathological and healthy posteromedial meniscus revealed opposite patterns in both T1Gd and ΔR1 values between pathological meniscus grade 2 and grade 3. The concentration of the contrast agent was lower than in healthy meniscus in grade 2 lesions (p = 0.046) but tended to increase in grade 3 lesions (p = 0.110). Maximum concentration of contrast agent was reached after 180 min in both cartilage and menisci (except for grade 3 menisci where the maximum concentration was reached after 90 min). Conclusion: dGEMRIM and dGEMRIC may be feasible to combine in vivo, preferably with one examination before and one 2 h after contrast injection. Possible different dGEMRIM patterns at different stages of meniscus lesions must be taken into account when evaluating meniscus pathology

Three-dimensional hip cartilage quality assessment of morphology and dGEMRIC by planar maps and automated segmentation.

The quantitative interpretation of hip cartilage magnetic resonance imaging (MRI) has been limited by the difficulty of identifying and delineating the cartilage in a three-dimensional (3D) dataset, thereby reducing its routine usage. In this paper a solution is suggested by unfolding the cartilage to planar two-dimensional (2D) maps on which both morphology and biochemical degeneration patterns can be investigated across the entire hip joint