Feasibility of automated 3-dimensional magnetic resonance imaging pancreas segmentation

Purpose: With the advent of magnetic resonance imaging (MRI) guided radiation therapy, internal organ motion can be imaged simultaneously during treatment. In this study, we evaluate the feasibility of pancreas MRI segmentation using state-of-the-art segmentation methods. Methods and materials: T2-weighted half-Fourier acquisition single-shot turbo spin-echo and T1 weighted volumetric interpolated breath-hold examination images were acquired on 3 patients and 2 healthy volunteers for a total of 12 imaging volumes. A novel dictionary learning (DL) method was used to segment the pancreas and compared to t mean-shift merging, distance regularized level set, and graph cuts, and the segmentation results were compared with manual contours using Dice's index, Hausdorff distance, and shift of the center of the organ (SHIFT). Results: All volumetric interpolated breath-hold examination images were successfully segmented by at least 1 of the autosegmentation method with Dice's index >0.83 and SHIFT ≤2 mm using the best automated segmentation method. The automated segmentation error of half-Fourier acquisition single-shot turbo spin-echo images was significantly greater. DL is statistically superior to the other methods in Dice’s overlapping index. For the Hausdorff distance and SHIFT measurement, distance regularized level set and DL performed slightly superior to the graph cuts method, and substantially superior to mean-shift merging. DL required least human supervision and was faster to compute. Conclusions: Our study demonstrated potential feasibility of automated segmentation of the pancreas on MRI scans with minimal human supervision at the beginning of imaging acquisition. The achieved accuracy is promising for organ localization

Cochlea-sparing acoustic neuroma treatment with 4π radiation therapy

Purpose: This study investigates whether 4π noncoplanar radiation therapy can spare the cochleae and consequently potentially improve hearing preservation in patients with acoustic neuroma who are treated with radiation therapy. Methods and materials: Clinical radiation therapy plans for 30 patients with acoustic neuroma were included (14 stereotactic radiation surgery [SRS], 6 stereotactic radiation therapy [SRT], and 10 intensity modulated radiation therapy [IMRT]). The 4π plans were created for each patient with 20 optimal beams selected using a greedy column generation method and subsequently recalculated in Eclipse for comparison. Organ-at-risk (OAR) doses, homogeneity index, conformity, and tumor control probability (TCP) were compared. Normal tissue complication probability (NTCP) was calculated for sensorineural hearing loss (SNHL) at 3 and 5 years posttreatment. The dose for each plan was then escalated to achieve 99.5% TCP. Results: 4π significantly reduced the mean dose to both cochleae by 2.0 Gy (32%) for SRS, 3.2 Gy (29%) for SRT, and 10.0 Gy (32%) for IMRT. The maximum dose to both cochleae was also reduced with 4π by 1.6 Gy (20%), 2.2 Gy (15%), and 7.1 Gy (18%) for SRS, SRT, and IMRT plans, respectively. The reductions in mean/maximum brainstem dose with 4π were also statistically significant. Mean doses to other OARs were reduced by 19% to 56% on average. 4π plans had a similar CN and TCP, with a significantly higher average homogeneity index (0.93 vs 0.92) and significantly lower average NTCP for SNHL at both 3 years (30.8% vs 40.8%) and 5 years (43.3% vs 61.7%). An average dose escalation of approximately 116% of the prescription dose achieved 99.5% TCP, which resulted in 32.6% and 43.4% NTCP for SNHL at 3 years and 46.4% and 64.7% at 5 years for 4π and clinical plans, respectively. Conclusions: Compared with clinical planning methods, optimized 4π radiation therapy enables statistically significant sparing of the cochleae in acoustic neuroma treatment as well as lowering of other OAR doses, potentially reducing the risk of hearing loss

Viability of Noncoplanar VMAT for liver SBRT compared with coplanar VMAT and beam orientation optimized 4π IMRT

Purpose: The 4π static noncoplanar radiation therapy delivery technique has demonstrated better normal tissue sparing and dose conformity than the clinically used volumetric modulated arc therapy (VMAT). It is unclear whether this is a fundamental limitation of VMAT delivery or the coplanar nature of its typical clinical plans. The dosimetry and the limits of normal tissue toxicity constrained dose escalation of coplanar VMAT, noncoplanar VMAT and 4π radiation therapy are quantified in this study. Methods and materials: Clinical stereotactic body radiation therapy plans for 20 liver patients receiving 30 to 60 Gy using coplanar VMAT (cVMAT) were replanned using 3 to 4 partial noncoplanar arcs (nVMAT) and 4π with 20 intensity modulated noncoplanar fields. The conformity number, homogeneity index, 50% dose spillage volume, normal liver volume receiving >15 Gy, dose to organs at risk (OARs), and tumor control probability were compared for all 3 treatment plans. The maximum tolerable dose yielding a normal liver normal tissue control probability <1%, 5%, and 10% was calculated with the Lyman-Kutcher-Burman model for each plan as well as the resulting survival fractions at 1, 2, 3, and 4 years. Results: Compared with cVMAT, the nVMAT and 4π plans reduced liver volume receiving >15 Gy by an average of 5 cm3 and 80 cm3, respectively. 4π reduced the 50% dose spillage volume by ∼23% compared with both VMAT plans, and either significantly decreased or maintained OAR doses. The 4π maximum tolerable doses and survival fractions were significantly higher than both cVMAT and nVMAT (P < .05) for all normal liver normal tissue control probability limits used in this study. Conclusions: The 4π technique provides significantly better OAR sparing than both cVMAT and nVMAT and enables more clinically relevant dose escalation for tumor local control. Therefore, despite the current accessibility of nVMAT, it is not a viable alternative to 4π for liver SBRT

Weak Magnetic Fields Enhance the Efficacy of Radiation Therapy

Purpose: The clinical efficacy of radiation therapy is mechanistically linked to ionization-induced free radicals that cause cell and tissue injury through direct and indirect mechanisms. Free radical reaction dynamics are influenced by many factors and can be manipulated by static weak magnetic fields (WMF) that perturb singlet-triplet state interconversion. Our study exploits this phenomenon to directly increase ionizing radiation (IR) dose absorption in tumors by combining WMF with radiation therapy as a new and effective method to improve treatment. Methods and Materials: Coils were custom made to produce both homogeneous and gradient magnetic fields. The gradient coil enabled simultaneous in vitro assessment of free radical/reactive oxygen species reactivity across multiple field strengths from 6 to 66 G. First, increases in IR-induced free radical concentrations using oxidant-sensitive fluorescent dyes in a cell-free system were measured and verified. Next, human and murine cancer cell lines were evaluated in in vitro and in vivo models after exposure to clinically relevant doses of IR in combination with WMF. Results: Cellular responses to IR and WMF were field strength and cell line dependent. WMF was able to enhance IR effects on reactive oxygen species formation, DNA double-strand break formation, cell death, and tumor growth. Conclusions: We demonstrate that the external presence of a magnetic field enhances radiation-induced cancer cell injury and death in vitro and in vivo. The effect extends beyond the timeframe when free radicals are induced in the presence of radiation into the window when endogenous free radicals are produced and therefore extends the applicability of this novel adjunct to cancer therapy in the context of radiation treatment

Aged Human Multipotent Mesenchymal Stromal Cells Can Be Rejuvenated by Neuron-Derived Neurotrophic Factor and Improve Heart Function After Injury

Reduced regenerative capacity of aged stem cells hampers the benefits of autologous cell therapy for cardiac regeneration. This study investigated whether neuron-derived neurotrophic factor (NDNF) could rejuvenate aged human bone marrow (hBM)- multipotent mesenchymal stromal cells (MSCs) and whether the rejuvenated hBM-MSCs could improve cardiac repair after ischemic injury. Over-expression of NDNF in old hBM-MSCs decreased cell senescence and apoptosis. Engraftment of NDNF over-expressing old hBM-MSCs into the ischemic area of mouse hearts resulted in improved cardiac function after myocardial infarction, while promoting implanted stem cell survival. Our findings suggest NDNF could be a new factor to rejuvenate aged stem cells and improve their capability to repair the aged heart after injury