Patient-specific quality assurance strategies for synthetic computed tomography in magnetic resonance-only radiotherapy of the abdomen.

Background and purpose: The superior tissue contrast of magnetic resonance (MR) compared to computed tomography (CT) led to an increasing interest towards MR-only radiotherapy. For the latter, the dose calculation should be performed on a synthetic CT (sCT). Patient-specific quality assurance (PSQA) methods have not been established yet and this study aimed to assess several software-based solutions. Materials and methods: A retrospective study was performed on 20 patients treated at an MR-Linac, which were selected to evenly cover four subcategories: (i) standard, (ii) air pockets, (iii) lung and (iv) implant cases. The neural network (NN) CycleGAN was adopted to generate a reference sCT, which was then compared to four PSQA methods: (A) water override of body, (B) five tissue classes with bulk densities, (C) sCT generated by a separate NN (pix2pix) and (D) deformed CT. Results: The evaluation of the dose endpoints demonstrated that while all methods A-D provided statistically equivalent results (p = 0.05) within the 2% level for the standard cases (i), only the methods C-D guaranteed the same result over the whole cohort. The bulk densities override was shown to be a valuable method in absence of lung tissue within the beam path. Conclusion: The observations of this study suggested that the use of an additional sCT generated by a separate NN was an appropriate tool to perform PSQA of a sCT in an MR-only workflow at an MR-Linac. The time and dose endpoints requirements were respected, namely within 10 min and 2%.

Synthetic computed tomography for low-field magnetic resonance-guided radiotherapy in the abdomen.

Background and purpose: The requirement of computed tomography (CT) for radiotherapy planning may be bypassed by synthetic CT (sCT) generated from magnetic resonance (MR), which has recently led to the clinical introduction of MR-only radiotherapy for specific sites. Further developments are required for abdominal sCT, mostly due to the presence of mobile air pockets affecting the dose calculation. In this study we aimed to overcome this limitation for abdominal sCT at a low field (0.35 T) hybrid MR-Linac. Materials and methods: A retrospective analysis was conducted enrolling 168 patients corresponding to 215 MR-CT pairs. After the exclusion criteria, 152 volumetric images were used to train the cycle-consistent generative adversarial network (CycleGAN) and 34 to test the sCT. Image similarity metrics and dose recalculation analysis were performed. Results: The generated sCT faithfully reproduced the original CT and the location of the air pockets agreed with the MR scan. The dose calculation did not require manual bulk density overrides and the mean deviations of the dose-volume histogram dosimetric points were within 1 % of the CT, without any outlier above 2 %. The mean gamma passing rates were above 99 % for the 2 %/ 2 mm analysis and no cases below 95 % were observed. Conclusions: This study presented the implementation of CycleGAN to perform sCT generation in the abdominal region for a low field hybrid MR-Linac. The sCT was shown to correctly allocate the electron density for the mobile air pockets and the dosimetric analysis demonstrated the potential for future implementation of MR-only radiotherapy in the abdomen.

Peptides and Astroglia Improve the Regenerative Capacity of Alginate Gels in the Injured Spinal Cord.

IMPACT STATEMENT: Axonal bridging across a lesion in the injured spinal cord requires a growth substrate and guidance cues. Using alginate hydrogels with capillary channels we show that poly-l-ornithine and laminin can be stably bound and improve cell adhesion and neurite growth in vitro, and axon growth in vivo by enhancing host cell infiltration in the injured spinal cord. Filling of coated hydrogels with postnatal astrocytes further increases short-distance axon growth and results in a continuous astroglial substrate across the host/graft interface. Thus, positively charged bioactive molecules can be stably bound to anisotropic capillary alginate hydrogels and early astrocytes further promote tissue integration.

Reconstructive kidney surgery for organ-preserving therapy of renal tumors.

BACKGROUND: The objective of this study was to evaluate differences in various clinical endpoints in patients with reconstructive surgery by renal partial nephrectomy for tumors up to 4 cm compared to tumors larger than 4 cm. MATERIAL AND METHODS: A total of 170 partial renal resection patients that presented malignant tumors were included in the retrospective study. Data was analyzed retrospectively based on internal clinic files, as well as a questionnaire to enhance the follow-up clinical outcomes data obtained. The most important outcomes determined included post-operative renal function, intra- and post-operative complications, local recurrence rate and total survival time. RESULTS: The local recurrence rate was 6.1% for tumors up to 4 cm in size, compared to 14.9% for tumors that were larger than 4 cm. Compared to results for partial resection of T1a tumors, results for partial resection of tumors larger than 4 cm are worse in terms of post-operative renal function (p=0.007), as well as in terms of a total complications rate (p=0.048). It is important to note that there was not only a higher risk of post-operative bleeding that required transfusions (p=0.012), but also a higher risk of a hypertensive episode during the post-operative period reviewed (p=0.022). In addition, the total survival time for patients presenting tumors of up to 4 cm in size was significantly better (p=0.003). CONCLUSION: The results of our retrospective study of 170 patients that underwent partial renal resection after the diagnosis of malignant tumors, is that partial renal resection presents an oncologicaly safe surgical solution with low local recurrence rates. Additionally, partial resection in case of tumors that are larger than 4 cm showed worse post-operative renal function, a higher complications rate and a worse survival rate.

Cell-seeded alginate hydrogel scaffolds promote directed linear axonal regeneration in the injured rat spinal cord.

Despite recent progress in enhancing axonal growth in the injured spinal cord, the guidance of regenerating axons across an extended lesion site remains a major challenge. To determine whether regenerating axons can be guided in rostrocaudal direction, we implanted 2mm long alginate-based anisotropic capillary hydrogels seeded with bone marrow stromal cells (BMSCs) expressing brain-derived neurotrophic factor (BDNF) or green fluorescent protein (GFP) as control into a C5 hemisection lesion of the rat spinal cord. Four weeks post-lesion, numerous BMSCs survived inside the scaffold channels, accompanied by macrophages, Schwann cells and blood vessels. Quantification of axons growing into channels demonstrated 3-4 times more axons in hydrogels seeded with BMSCs expressing BDNF (BMSC-BDNF) compared to control cells. The number of anterogradely traced axons extending through the entire length of the scaffold was also significantly higher in scaffolds with BMSC-BDNF. Increasing the channel diameters from 41µm to 64µm did not lead to significant differences in the number of regenerating axons. Lesions filled with BMSC-BDNF without hydrogels exhibited a random axon orientation, whereas axons were oriented parallel to the hydrogel channel walls. Thus, alginate-based scaffolds with an anisotropic capillary structure are able to physically guide regenerating axons. STATEMENT OF SIGNIFICANCE: After injury, regenerating axons have to extend across the lesion site in the injured spinal cord to reestablish lost neuronal connections. While cell grafting and growth factor delivery can promote growth of injured axons, without proper guidance, axons rarely extend across the lesion site. Here, we show that alginate biomaterials with linear channels that are filled with cells expressing the growth-promoting neurotrophin BDNF promote linear axon extension throughout the channels after transplantation to the injured rat spinal cord. Animals that received the same cells but no alginate guidance structure did not show linear axonal growth and axons did not cross the lesion site. Thus, alginate-based scaffolds with a capillary structure are able to physically guide regenerating axons.

AngleJ: A new tool for the automated measurement of neurite growth orientation in tissue sections.

BACKGROUND: Regeneration of axons is one means to restore function after central nervous system and peripheral nervous system injury. Besides increasing the number of regenerating axons, guidance of axons over long distances into and across a lesion site are important determinants for efficient functional restoration. Quantification of axon growth directions is therefore an important measure for the efficacy of neuroregenerative approaches. While several methods exist to manually or automatically trace neurites in images of neuronal cultures to determine their length, tools to automatically measure the effect of neurite guidance in tissue sections do not exist. NEW METHOD: Because manual measurements of the orientation of regenerating axons are labor-intensive, time-consuming and unreliable, a plugin called AngleJ for the open source software ImageJ was developed that automatically determines axonal orientation in images of immunohistochemically labeled sections of the spinal cord. RESULTS: Given user-defined filters and thresholds, the plugin accurately detects neurites in sections of the intact spinal cord white matter and a spinal cord hemisection lesion model and measures the distribution pattern of axonal angles. COMPARISON WITH EXISTING METHODS: Values of automatically measured angles strongly correlate with angles obtained by manual measurements in ImageJ (Pearson correlation 0.88-0.97 for white matter and 0.76-0.94 for axons sprouting into a lesion site). CONCLUSIONS: AngleJ can be used as a fast alternative to manual angle measurement in conjunction with ImageJ and its source code is freely available to the community.

Genetic determination of human facial morphology: links between cleft-lips and normal variation.

Recent genome-wide association studies have identified single nucleotide polymorphisms (SNPs) associated with non-syndromic cleft lip with or without cleft palate (NSCL/P), and other previous studies showed distinctly differing facial distance measurements when comparing unaffected relatives of NSCL/P patients with normal controls. Here, we test the hypothesis that genetic loci involved in NSCL/P also influence normal variation in facial morphology. We tested 11 SNPs from 10 genomic regions previously showing replicated evidence of association with NSCL/P for association with normal variation of nose width and bizygomatic distance in two cohorts from Germany (N=529) and the Netherlands (N=2497). The two most significant associations found were between nose width and SNP rs1258763 near the GREM1 gene in the German cohort (P=6 × 10(-4)), and between bizygomatic distance and SNP rs987525 at 8q24.21 near the CCDC26 gene (P=0.017) in the Dutch sample. A genetic prediction model explained 2% of phenotype variation in nose width in the German and 0.5% of bizygomatic distance variation in the Dutch cohort. Although preliminary, our data provide a first link between genetic loci involved in a pathological facial trait such as NSCL/P and variation of normal facial morphology. Moreover, we present a first approach for understanding the genetic basis of human facial appearance, a highly intriguing trait with implications on clinical practice, clinical genetics, forensic intelligence, social interactions and personal identity.

A novel approach to the detection of acromegaly: accuracy of diagnosis by automatic face classification.

CONTEXT: The delay between onset of first symptoms and diagnosis of the acromegaly is 6-10 yr. Acromegaly causes typical changes of the face that might be recognized by face classification software. OBJECTIVE: The objective of the study was to assess classification accuracy of acromegaly by face-classification software. DESIGN: This was a diagnostic study. SETTING: The study was conducted in specialized care. PARTICIPANTS: Participants in the study included 57 patients with acromegaly (29 women, 28 men) and 60 sex- and age-matched controls. INTERVENTIONS: We took frontal and side photographs of the faces and grouped patients into subjects with mild, moderate, and severe facial features of acromegaly by overall impression. We then analyzed all pictures using computerized similarity analysis based on Gabor jets and geometry functions. We used the leave-one-out cross-validation method to classify subjects by the software. Additionally, all subjects were classified by visual impression by three acromegaly experts and three general internists. MAIN OUTCOME MEASURE: Classification accuracy by software, experts, and internists was measured. FINDINGS: The software correctly classified 71.9% of patients and 91.5% of controls. Classification accuracy for patients by visual analysis was 63.2 and 42.1% by experts and general internists, respectively. Classification accuracy for controls was 80.8 and 87.0% by experts and internists, respectively. The highest differences in accuracy between software and experts and internists were present for patients with mild acromegaly. CONCLUSIONS: Acromegaly can be detected by computer software using photographs of the face. Classification accuracy by software is higher than by medical experts or general internists, particularly in patients with mild features of acromegaly. This is a promising tool to help detecting acromegaly.