Detectability and intra-fraction motion of individual elective lymph nodes in head and neck cancer patients on the Magnetic Resonance Image guided linear accelerator.

Background and purpose: Individual elective lymph node irradiation instead of elective neck irradiation is a new concept for head-and-neck cancer (HNC) patients developed for the Magnetic Resonance Image guided linear accelerator (MR-linac). To prepare this, the detectability, volume changes and intra-fraction motion of elective lymph nodes on the MR-linac was assessed. Materials and methods: A total of 15 HNC patients underwent diagnostic pre-treatment MRI. Additionally, two MR-linac scans were obtained with a 10-minute time difference in the first week of radiation treatment. Elective lymph node contours inside lymph node levels (Ib-V) were segmented on the pre-treatment MRI and the MR-linac scans and compared on number and maximal transversal diameter. Intra-fraction motion of elective lymph nodes on the MR-linac was estimated using Center of Mass (COM) distances and incremental isotropic expansion of lymph node segmentations. Results: Of all 679 detected lymph nodes on the pre-treatment MRI, eight lymph nodes were not detectable on the first MR-linac scan and 16 new lymph nodes were detected. Lymph node diameters between the pre-treatment MRI scan and the MR-linac scan varied from -0.19 to + 0.13 mm. COM distances varied from 1.2 to 1.7 mm and lymph node contours had to be expanded with 3 mm. Conclusions: Nearly all elective lymph nodes were detectable on the 1.5T MR-linac scan with no major changes in target volumes compared to the pre-treatment MRI. Simulated intra-fraction motion during the MR-linac scans was smaller than the 5-mm margin that will be used in the first elective lymph node radiation treatment.

A perturbation approach for ultrafast calculation of RF field enhancements near medical implants in MRI.

Patients with medical implants often are deprived of magnetic resonance imaging examination because of safety risks. One specific risk is the enhancement of the radiofrequency fields around the medical implant potentially resulting in significant tissue heating and damage. The assessment of this enhancement is a computationally demanding task, with simulations taking hours or days to converge. Conventionally the source of the radiofrequency fields, patient anatomy, and the medical implant are simulated concurrently. To alleviate the computational burden, we reformulate a fast simulation method that views the medical implant as a small perturbation of the simulation domain without the medical implant and calculates the radiofrequency fields associated with this perturbation. Previously, this method required an extensive offline stage where the result is intractable for large simulation domains. Currently, this offline stage is no longer required and the method is completely online. The proposed method results in comparable radiofrequency fields but is orders of magnitude faster compared to standard simulation technique; the finite-difference time-domain, the finite-sums, and the finite element methods. This acceleration could enable patient-specific and potentially online radiofrequency safety assessment.

MRI visibility and displacement of elective lymph nodes during radiotherapy in head and neck cancer patients.

Background and purpose: To decrease the impact of radiotherapy to healthy tissues in the head and neck region, we propose to restrict the elective neck irradiation to elective lymph nodes at risk of containing micro metastases instead of the larger lymph node volumes. To assess whether this new concept is achievable in the clinic, we determined the number, volume changes and displacement of elective lymph nodes during the course of radiotherapy. Materials and methods: MRI scans of 10 head and neck cancer (HNC) patients were acquired before radiotherapy and in week 2, 3, 4 and 5 during radiotherapy. The weekly delineations of elective lymph nodes inside the lymph node levels (Ib/II/III/IVa/V) were rigidly registered and analyzed regarding number and volume. The displacement of elective lymph nodes was determined by center of mass (COM) distances, vector-based analysis and the isotropic contour expansion of the lymph nodes of the pre-treatment scan or the scan of the previous week in order to geographically cover 95% of the lymph nodes in the scans of the other weeks. Results: On average, 31 elective lymph nodes in levels Ib-V on each side of the neck were determined. This number remained constant throughout radiotherapy in most lymph node levels. The volume of the elective lymph nodes reduced significantly in all weeks, up to 50% in week 5, compared to the pre-treatment scan. The largest median COM displacements were seen in level V, for example 5.2 mm in week 5 compared to the pre-treatment scan. The displacement of elective lymph nodes was mainly in cranial direction. Geographical coverage was obtained when the lymph node volumes were expanded with 7 mm in case the pre-treatment scan was used and 6.5 mm in case the scan of the previous week was used. Conclusion: Elective lymph nodes of HNC patients remained visible on MRI and decreased in size during radiotherapy. The displacement of elective lymph nodes differ per lymph node level and were mainly directed cranially. Weekly adaptation does not seem to improve coverage of elective lymph nodes. Based on our findings we expect elective lymph node irradiation is achievable in the clinic.

A single setup approach for the MRI-based measurement and validation of the transfer function of elongated medical implants.

PURPOSE: To propose a single setup using the MRI to both measure and validate the transfer function (TF) of linear implants. Conventionally, the TF of an implant is measured in one bench setup and validated using another. METHODS: It has been shown that the TF can be measured using MRI. To validate this measurement, the implant is exposed to different incident electric fields, while the temperature increase at the tip is monitored. For a good validation, the incident electric fields that the implant is exposed to should be orthogonal. We perform a simulation study on six different methods that change the incident electric field. Afterward, a TF measurement and validation study using the best method from the simulations is performed. This is done with fiberoptic temperature probes at 1.5 T for four linear implant structures using the proposed single setup. RESULTS: The simulation study showed that positioning local transmit coils at different locations along the lead trajectory has a similar validation quality compared with changing the implant trajectory (ie, the conventional validation method). For the validation study that was performed, an R2 ≥ 0.91 was found for the four investigated leads. CONCLUSION: A single setup to both measure and validate the transfer function using local transmit coils has been shown to work. The benefits of using the proposed validation method are that there is only one setup required instead of two and the implant trajectory is not varied; therefore, the relative distance between the leap tip and the temperature probe is constant.

Transceive phase corrected 2D contrast source inversion-electrical properties tomography.

PURPOSE: To remove the necessity of the tranceive phase assumption for CSI-EPT and show electrical properties maps reconstructed from measured data obtained using a standard 3T birdcage body coil setup. METHODS: The existing CSI-EPT algorithm is reformulated to use the transceive phase rather than relying on the transceive phase assumption. Furthermore, the radio frequency (RF)-shield is numerically implemented to accurately model the RF fields inside the MRI scanner. We verify that the reformulated two-dimensional (2D) CSI-EPT algorithm can reconstruct electrical properties maps given 2D electromagnetic simulations. Afterward, the algorithm is tested with three-dimensional (3D) FDTD simulations to investigate if the 2D CSI-EPT can retrieve the electrical properties for 3D RF fields. Finally, an MR experiment at 3T with a phantom is performed. RESULTS: From the results of the 2D simulations, it is seen that CSI-EPT can reconstruct the electrical properties using MRI accessible quantities. For 3D simulations, it is observed that the electrical properties are underestimated, nonetheless, CSI-EPT has a lower standard deviation than the standard Helmholtz based methods. Finally, the first CSI-EPT reconstructions based on measured data are presented showing comparable accuracy and precision to reconstructions based on simulated data, and demonstrating the feasibility of CSI-EPT. CONCLUSIONS: The CSI-EPT algorithm was rewritten to use MRI accessible quantities. This allows for CSI-EPT to fully exploit the benefits of the higher static magnetic field strengths with a standard quadrature birdcage coil setup.

Statins, diabetes mellitus and prognosis of amyotrophic lateral sclerosis: data from 501 patients of a population-based registry in southwest Germany.

BACKGROUND AND PURPOSE: A wide variety of metabolic changes, including an increased incidence of diabetes mellitus (DM) and dyslipidaemia, has been described in amyotrophic lateral sclerosis (ALS). The aim of this study was to investigate the associations of statin use and history of DM with onset of disease and survival in patients with ALS. METHODS: In all, 501 patients (mean age 65.2 ± 10.9 years; 58.5% male) from the ALS Registry Swabia recruited between October 2010 and April 2016 were included in this prospective cohort study. Data were collected using a standardized questionnaire. RESULTS: Statin use (n = 65) was not associated with overall survival (P = 0.62). Age of ALS onset in patients with DM was 4.2 years later (95% confidence interval 1.3-7.2 years) than in patients without DM (P < 0.01). The overall survival of patients with high body mass index at study entry (>27.0 kg/m2 , upper quartile, n = 127) was prolonged by more than 5 months compared to patients with low body mass index (<22.0 kg/m2 , lower quartile, n = 123; P = 0.04). CONCLUSIONS: This study supports the view that statin use is not associated with overall survival of ALS patients, suggesting that statins are not harmful and should not be discontinued in ALS. Furthermore, the delayed onset of ALS in patients with DM may mirror the potentially protective metabolic profile associated with type 2 DM. Consistently, this study provides further evidence that high body mass index is a positive prognostic factor in ALS.

Accelerating implant RF safety assessment using a low-rank inverse update method.

PURPOSE: Patients who have medical metallic implants, e.g. orthopaedic implants and pacemakers, often cannot undergo an MRI exam. One of the largest risks is tissue heating due to the radio frequency (RF) fields. The RF safety assessment of implants is computationally demanding. This is due to the large dimensions of the transmit coil compared to the very detailed geometry of an implant. METHODS: In this work, we explore a faster computational method for the RF safety assessment of implants that exploits the small geometry. The method requires the RF field without an implant as a basis and calculates the perturbation that the implant induces. The inputs for this method are the incident fields and a library matrix that contains the RF field response of every edge an implant can occupy. Through a low-rank inverse update, using the Sherman-Woodbury-Morrison matrix identity, the EM response of arbitrary implants can be computed within seconds. We compare the solution from full-wave simulations with the results from the presented method, for two implant geometries. RESULTS: From the comparison, we found that the resulting electric and magnetic fields are numerically equivalent (maximum error of 1.35%). However, the computation was between 171 to 2478 times faster than the corresponding GPU accelerated full-wave simulation. CONCLUSIONS: The presented method enables for rapid and efficient evaluation of the RF fields near implants and might enable situation-specific scanning conditions.

Bone mineral density and breast cancer risk: Results from the Vorarlberg Health Monitoring & Prevention Program and meta-analysis.

We investigated the association between bone mineral density (BMD) and breast cancer risk in a large prospective cohort and quantified the evidence in a meta-analysis of prospective studies. Baseline BMD has been measured by dual energy X-ray absorptiometry (DXA, N = 1418). Data on medication and lifestyle has been collected by questionnaire. Cox proportional Hazards models were applied to calculate Hazard Ratios for breast cancer. In addition, a meta-analysis on categorical and dose-response values including the current results has been performed applying random-effects models. During mean follow-up of 16.3 (SD 3.3) years of 1380 women (mean age 55.5 ± 6.3 years), 52 cases of invasive breast cancer were identified. We found no statistically significant association of BMD with breast cancer risk (per one z-score increase, HR 0.91, 95% CI 0.67-1.23). In the meta-analysis, however, breast cancer risk increased by 15% and 16% per 0.1 g/m2 increase in BMD at the lumbar spine (95% CI 0.99-1.33) and at the femoral neck (95% CI 1.02-1.32), respectively. Compared to the lowest, the HRs for breast cancer were statistically significant for the highest BMD category, i.e. 1.49 (95% CI 1.04-2.13) at the lumbar spine and 1.66 (95% CI 1.26-2.18) at the femur. We found no association between BMD (DXA) and breast cancer risk in our cohort. However, overall the present meta-analysis extends and confirms the statistically significant association between increasing BMD and increased breast cancer risk.

The effect of age on the shape of the BMI-mortality relation and BMI associated with minimum all-cause mortality in a large Austrian cohort.

BACKGROUND: It is unclear if the body mass index (BMI) associated with minimum all-cause mortality is constant throughout adult life or increasing with age. METHODS: We applied multivariable fractional polynomials to the data of the Vorarlberg Health Monitoring and Prevention Program to quantify the BMI associated with minimum mortality over age. The analysis included data of 129,904 never-smoking women and men (mean age: 45.4 years) who were followed for a median of 18.6 years. RESULTS: Optimum BMI in women increased with age, lying within the normal BMI category (according to the World Health Organization definition) from the age of 20 years (23.3 kg m(-2), 95% confidence interval (CI): 22.2-24.3) to the age of 54 years and in the lower half of the overweight category from the age of 55 years onwards, reaching 26.2 kg m(-2) (95% CI: 25.1-27.3) at the age of 69 years. In men, optimum BMI increased slightly from 23.7 kg m(-2) (95% CI: 22.1-25.2) at the age of 20 years until the age of 59 years, reaching a BMI of 25.4 kg m(-2) (95% CI: 24.8-26.0) and decreased afterwards to 22.7 kg m(-2) (95% CI: 20.9-24.6) at the age of 80 years. CONCLUSIONS: Our results indicate that BMI associated with minimum all-cause mortality changes with age and that patterns differ by sex. Sex- and age-independent BMI recommendations might therefore be inappropriate. Further studies using flexible methods instead of predefined categories are necessary to revise BMI recommendations.

Effect of germination and autoclaving of sprouted finger millet and kidney beans on cyanide content.

Cyanide contents of locally purchased brown finger millet (Eleusine corocana L. Gaertner) and brown speckled kidney bean seeds (Phaseolus vulgaries var. Rose Coco) were determined using raw, germinated and autoclaved samples. The aim was to establish the extent of cyanide content increase resulting from the germination process and the effectiveness of the autoclaving process on the reduction of cyanide levels in the samples, for safety considerations. Autoclaving was carried out at 121degree C for 20 minutes. It was found that germination increased the cyanide content by 2.11 to 2.14 fold in finger millet for laboratory processed samples. In the case of kidney beans the increment was 1.76 to 1.77 fold for laboratory samples. The increments for field processed samples were in the same range as those for laboratory samples. Autoclaving reduced the cyanide content to between 61.8 and 65.9 % of the original raw contents for finger millet and between 56.6 to 57.8% in the case of kidney beans. The corresponding reductions for field samples were also found to be within the same ranges as the laboratory processed samples. It was concluded that autoclaving significantly reduced the cyanide levels in germinated finger millet and kidney beans.

Evaluation of the nutritional characteristics of a finger millet based complementary food.

Finger millet (Eleusine coracana), kidney beans (Phaseolus vulgaris), peanuts (Arachis hypogoea), and mango (Mangifera indica) were processed separately and then combined, on the basis of their amino acid scores and energy content, into a complementary food for children of weaning age. The finger millet and kidney beans were processed by germination, autoclaving, and lactic acid fermentation. A mixture containing, on a dry matter basis, 65.2, 19.1, 8.0, and 7.7% of the processed finger millet, kidney beans, peanuts, and mango, respectively, gave a composite protein with an in vitro protein digestibility of 90.2% and an amino acid chemical score of 0.84. This mixture had an energy density of 16.3 kJ.g(-1) of dry matter and a decreased antinutrient content and showed a measurable improvement in the in vitro extractability for calcium, iron, and zinc. A 33% (w/v) pap made from a mix of the processed ingredients had an energy density of 5.4 kJ.g(-1) of pap, which is sufficient to meet the energy requirements of well-nourished children of 6-24 months of age at three servings a day and at the FAO average breast-feeding frequency.

Rectal bleeding after conformal 3D treatment of prostate cancer: time to occurrence, response to treatment and duration of morbidity.

PURPOSE: Rectal bleeding is the most common late sequelae of high-dose 3D conformal treatment (3DCRT) for prostate cancer and may limit attempts to improve local control by dose escalation. The clinical course of this complication is reported including time to onset, response to treatment, duration of morbidity, and multivariate analysis for predictors. METHODS AND MATERIALS: From March 1989 to June 1995, 670 patients with prostate cancer were treated with 3DCRT at Fox Chase Cancer Center. Eighty-nine patients developed Grade 2 or Grade 3 complications due to rectal bleeding and are analyzed. Multivariate analysis results for predictors of Grade 2 and 3 rectal bleeding are reported as well as time to development, response to initial and retreatment, and duration of morbidity. RESULTS: The median time to occurrence is not significantly different (p = 0.09) for Grade 2 (13 months, range 4-41 months) compared to Grade 3 rectal bleeding (18 months, range 4-40 months), while the corresponding median duration of symptoms was significantly different (p < 0.0001) being 1 month (range 1-12) vs. 10 months (1-34) for Grade 2 and Grade 3 bleeding, respectively. For Grade 2 bleeding, medication or coagulation was highly effective as initial or retreatment resolving 66 of 73 patients. For Grade 3 bleeding, three patients responded without medication following blood transfusion only, while with multiple coagulations and medication 12 of 16 patients improved to < or = Grade 1. Multivariate analysis demonstrates that dose is the only significant factor associated with Grade 2 (p = 0.01) or Grade 3 (p = 0.01) rectal bleeding. Of seven nonresponders to treatment for Grade 2 bleeding, three have died of intercurrent disease at 10, 19, and 26 months, while four are alive with continuing Grade 2 bleeding at 12, 14, 15, and 30 months after onset. The four nonresponders to treatment for Grade 3 bleeding continue to bleed 1, 9, 32, and 35 months after the third coagulation despite continuing care. CONCLUSIONS: Chronic rectal bleeding is a sequelae of high-dose conformal treatment of prostate cancer. Grade 2 morbidity responds to medication or limited coagulation (< or = 2) in 90% of patients. Grade 3 morbidity responds to medication and multiple coagulations (> or = 3) in 75% of patients. The chronicity of Grade 3 morbidity is illustrated by a 10-month median duration for response to treatment, with a range of response extending to 34 months. Nonresponders to treatment have continued to bleed up to 35 months after the third coagulation. Appropriate shielding of the rectal mucosa limiting dose to < 72 Gy is required to avoid a high incidence of these complications, as dose is the only significant variable associated with rectal bleeding.

Chronic rectal bleeding after high-dose conformal treatment of prostate cancer warrants modification of existing morbidity scales.

PURPOSE: Serious late morbidity (Grade 3/4) from the conformal treatment of prostate cancer has been reported in <1% to 6% of patients based on existing late gastrointestinal (GI) morbidity scales. None of the existing morbidity scales include our most frequently observed late GI complication, which is chronic rectal bleeding requiring multiple fulgerations. This communication documents the frequency of rectal bleeding requiring multiple fulgerations and illustrates the variation in reported late serious GI complication rates by the selection of morbidity scale. METHODS AND MATERIALS: Between May 1989 and December 1993, 352 patients with T1-T3 nonmetastatic prostate cancers were treated with our four-field conformal technique without special rectal blocking. This technique includes a 1-cm margin from the clinical target volume (CTV) to the planning target volume (PTV) in all directions. The median follow-up for these patients was 36 months (range 2-76), and the median center of prostate dose was 74 Gy (range 63-81). Three morbidity scales are assessed: the Radiation Therapy Oncology Group (RTOG), the Late Effects Normal Tissue Task Force (LENT), and our modification of the LENT (FC-LENT). This modification registers chronic rectal bleeding requiring at least one blood transfusion and/or more than two coagulations as a Grade 3 event. Estimates for Grade 3/4 late GI complication rates were determined using Kaplan-Meier methodology. The duration of severe symptoms with chronic rectal bleeding is measured from the first to the last transrectal coagulation. Latency is measured from the end of radiotherapy to surgery, first blood transfusion, or third coagulation procedure. RESULTS: Sixteen patients developed Grade 3/4 complications by one of the three morbidity scales. Two patients required surgery (colostomy or sigmoid resection), three required multiple blood transfusions, two required one or two blood transfusions, and nine required at least three coagulations. The median duration of bleeding for those patients requiring multiple procedures was 7 months (range 3-33) and the median latency was 22 months (range 9-40). The 5-year actuarial rate of Grade 3/4 complications by each scale are: RTOG 0.7%, LENT 2%, and FC-LENT 6%. The rate of chronic rectal bleeding increases with increasing dose and is low in patients treated with conventional techniques owing to lower doses. CONCLUSION: Chronic rectal bleeding requiring any blood transfusion(s) or multiple coagulation procedures is our most frequently observed complication. This complication appears late in follow-up and is present for a long duration. We believe this justifies the inclusion of chronic rectal bleeding requiring multiple coagulation procedures as a Grade 3 event in future morbidity scales. Our data illustrate that published Grade 3/4 morbidity rates are highly dependent on the morbidity scale selected, as our data show 0.7% RTOG, 2% LENT, and 6% FC-LENT. Obviously, a uniform scale is required that includes the newly recognized serious late effects associated with the conformal treatment of prostate cancer.

Late GI and GU complications in the treatment of prostate cancer.

PURPOSE: To assess the factors that predict late GI and GU morbidity in radiation treatment of the prostate. METHODS AND MATERIALS: Seven hundred twelve consecutive prostate cancer patients treated at this institution between 1986 and 1994 (inclusive) with conformal or conventional techniques were included in the analysis. Patients had at least 3 months follow-up and received at least 65 Gy. Late GI Grade 3 morbidity was rectal bleeding (requiring three or more procedures) or proctitis. Late Grade 3 GU morbidity was cystitis or stricture. Multivariate analysis (MVA) was used to assess factors related to the complication-free survival. The factors assessed were age, occurrence of side effects > or = Grade 2 during treatment, irradiated volume parameters (use of pelvic fields, treatment of seminal vesicles to full dose or 57 Gy, and use of additional rectal shielding), dose, comorbidities, and other treatments (hormonal manipulation, TURP). RESULTS: Acute GI and GU side effects (Grade 2 or higher) were noted in 246 and 201 patients, respectively; 67 of these patients exhibited both. GI side effects were not correlated with GU side effects acutely. Late and acute morbidities were correlated (both GI and GU). Fifteen of the 712 patients expressed Grade 3 or 4 GI injuries 3 to 32 months after the end of treatment, with a mean of 14.3 months. One hundred fifteen patients expressed Grade 2 or higher GI morbidity (mean: 13.7 months). The 43 Grade 2 or higher GU morbidities occurred significantly later (mean: 22.7 months). Central axis dose was the only independent variable significantly related to the incidence of late GI morbidity on MVA. No treatment volume parameters were significant for Grade 3. The following parameters were significantly related (by MVA) to Grade 2 GI morbidity: central axis dose, use of the increased rectal shielding, androgen deprivation therapy starting before RT. Acute and late GI morbidities were highly correlated. History of diabetes, treatment of pelvic nodes, and age less than 60 years were significantly related to acute GI side effects. The parameters significantly related to late Grade 2 or higher GU morbidity were central axis dose, androgen deprivation therapy (Zoladex or Lupron) prior to radiation therapy (RT), history of obstructive symptoms, and acute GU side effects. There were too few late Grade 3 GU morbidities to perform multivariate analysis. Acute GU side effects were highly correlated with late GU injury. The following were correlated with acute GU side effects: history of diabetes (+), treatment with conformal fields (-), TURP before RT (-), presentation with urinary obstructive symptoms. CONCLUSION: Both late GI and GU morbidity demonstrate a dose dependence, but only the volume dependence observed is a reduction in late Grade 2-4 GI morbidity by increasing the rectal shielding in the lateral fields for the final 10 Gy. Moreover, both late GI and GU morbidity was increased in patients treated with hormone manipulation prior to RT. GI and GU injuries were correlated with their corresponding acute side effects. GI and GU complications must not be combined for analysis to determine the factors related to their occurrence.