Deep learning for improving ZTE MRI images in free breathing.

INTRODUCTION: Despite a growing interest in lung MRI, its broader use in a clinical setting remains challenging. Several factors limit the image quality of lung MRI, such as the extremely short T2 and T2* relaxation times of the lung parenchyma and cardiac and breathing motion. Zero Echo Time (ZTE) sequences are sensitive to short T2 and T2* species paving the way to improved "CT-like" MR images. To overcome this limitation, a retrospective respiratory gated version of ZTE (ZTE4D) which can obtain images in 16 different respiratory phases during free breathing was developed. Initial performance of ZTE4D have shown motion artifacts. To improve image quality, deep learning with fully convolutional neural networks (FCNNs) has been proposed. CNNs has been widely used for MR imaging, but it has not been used for improving free-breathing lung imaging yet. Our proposed pipeline facilitates the clinical work with patients showing difficulties/uncapable to perform breath-holding, or when the different gating techniques are not efficient due to the irregular respiratory pace. MATERIALS AND METHODS: After signed informed consent and IRB approval, ZTE4D free breathing and breath-hold ZTE3D images were obtained from 10 healthy volunteers on a 1.5 T MRI scanner (GE Healthcare Signa Artist, Waukesha, WI). ZTE4D acquisition captured all 16 phases of the respiratory cycle. For the ZTE breath-hold, the subjects were instructed to hold their breath in 5 different inflation levels ranging from full expiration to full inspiration. The training dataset consisting of ZTE-BH images of 10 volunteers was split into 8 volunteers for training, 1 for validation and 1 for testing. In total 800 ZTE breath-hold images were constructed by adding Gaussian noise and performing image transformations (translations, rotations) to imitate the effect of motion in the respiratory cycle, and blurring from varying diaphragm positions, as it appears for ZTE4D. These sets were used to train a FCNN model to remove the artificially added noise and transformations from the ZTE breath-hold images and reproduce the original quality of the images. Mean squared error (MSE) was used as loss function. The remaining 2 healthy volunteer's ZTE4D images were used to test the model and qualitatively assess the predicted images. RESULTS: Our model obtained a MSE of 0.09% on the training set and 0.135% on the validation set. When tested on unseen data the predicted images from our model improved the contrast of the pulmonary parenchyma against air filled regions (airways or air trapping). The SNR of the lung parenchyma was quantitatively improved by a factor of 1.98 and the CNR lung- blood, which is indicating the visibility of the intrapulmonary vessels, was improved by 4.2%. Our network was able to reduce ghosting artifacts, such as diaphragm movement and blurring, and enhancing image quality. DISCUSSION: Free-breathing 3D and 4D lung imaging with MRI is feasible, however its quality is not yet acceptable for clinical use. This can be improved with deep learning techniques. Our FCNN improves the visual image quality and reduces artifacts of free-breathing ZTE4D. Our main goal was rather to remove ghosting artifacts from the ZTE4D images, to improve diagnostic quality of the images. As main results of the network, diaphragm contour increased with sharper edges by visual inspection and less blurring of the anatomical structures and lung parenchyma. CONCLUSION: With FCNNs, image quality of free breathing ZTE4D lung MRI can be improved and enable better visualization of the lung parenchyma in different respiratory phases.

A Multi-Center, Multi-Vendor Study to Evaluate the Generalizability of a Radiomics Model for Classifying Prostate cancer: High Grade vs. Low Grade.

Radiomics applied in MRI has shown promising results in classifying prostate cancer lesions. However, many papers describe single-center studies without external validation. The issues of using radiomics models on unseen data have not yet been sufficiently addressed. The aim of this study is to evaluate the generalizability of radiomics models for prostate cancer classification and to compare the performance of these models to the performance of radiologists. Multiparametric MRI, photographs and histology of radical prostatectomy specimens, and pathology reports of 107 patients were obtained from three healthcare centers in the Netherlands. By spatially correlating the MRI with histology, 204 lesions were identified. For each lesion, radiomics features were extracted from the MRI data. Radiomics models for discriminating high-grade (Gleason score ≥ 7) versus low-grade lesions were automatically generated using open-source machine learning software. The performance was tested both in a single-center setting through cross-validation and in a multi-center setting using the two unseen datasets as external validation. For comparison with clinical practice, a multi-center classifier was tested and compared with the Prostate Imaging Reporting and Data System version 2 (PIRADS v2) scoring performed by two expert radiologists. The three single-center models obtained a mean AUC of 0.75, which decreased to 0.54 when the model was applied to the external data, the radiologists obtained a mean AUC of 0.46. In the multi-center setting, the radiomics model obtained a mean AUC of 0.75 while the radiologists obtained a mean AUC of 0.47 on the same subset. While radiomics models have a decent performance when tested on data from the same center(s), they may show a significant drop in performance when applied to external data. On a multi-center dataset our radiomics model outperformed the radiologists, and thus, may represent a more accurate alternative for malignancy prediction.

Classification of Clinically Significant Prostate Cancer on Multi-Parametric MRI: A Validation Study Comparing Deep Learning and Radiomics.

The computer-aided analysis of prostate multiparametric MRI (mpMRI) could improve significant-prostate-cancer (PCa) detection. Various deep-learning- and radiomics-based methods for significant-PCa segmentation or classification have been reported in the literature. To be able to assess the generalizability of the performance of these methods, using various external data sets is crucial. While both deep-learning and radiomics approaches have been compared based on the same data set of one center, the comparison of the performances of both approaches on various data sets from different centers and different scanners is lacking. The goal of this study was to compare the performance of a deep-learning model with the performance of a radiomics model for the significant-PCa diagnosis of the cohorts of various patients. We included the data from two consecutive patient cohorts from our own center (n = 371 patients), and two external sets of which one was a publicly available patient cohort (n = 195 patients) and the other contained data from patients from two hospitals (n = 79 patients). Using multiparametric MRI (mpMRI), the radiologist tumor delineations and pathology reports were collected for all patients. During training, one of our patient cohorts (n = 271 patients) was used for both the deep-learning- and radiomics-model development, and the three remaining cohorts (n = 374 patients) were kept as unseen test sets. The performances of the models were assessed in terms of their area under the receiver-operating-characteristic curve (AUC). Whereas the internal cross-validation showed a higher AUC for the deep-learning approach, the radiomics model obtained AUCs of 0.88, 0.91 and 0.65 on the independent test sets compared to AUCs of 0.70, 0.73 and 0.44 for the deep-learning model. Our radiomics model that was based on delineated regions resulted in a more accurate tool for significant-PCa classification in the three unseen test sets when compared to a fully automated deep-learning model.

New diagnostic approach of the different types of isolated craniosynostosis.

In this study, we diagnose skull shape deformities by analysing sinusoid curves obtained from standardized computed tomography (CT) slices of the skull for the common craniosynostoses (scaphocephaly, brachycephaly, trigonocephaly, right- and left-sided anterior plagiocephaly). Scaphocephaly has a high forehead peak and low troughs, in contrast to brachycephaly. Anterior plagiocephaly has asymmetry and shifting of the forehead peak. Trigonocephaly has a high and narrow frontal peak. Control patients have a symmetrical skull shape with low troughs and a high and broader frontal peak. Firstly, we included 5 children of every group of the common craniosynostoses and additionally 5 controls for extraction and calculation of characteristics. A diagnostic flowchart was developed. Secondly, we included a total of 51 craniosynostosis patients to validate the flowchart. All patients were correctly classified using the flowchart.Conclusion: Our study proposes and implements a new diagnostic approach of craniosynostosis. We describe a diagnostic flowchart based on specific characteristics for every type of craniosynostosis related to the specific skull deformities and control patients. All variables are expressed in number; therefore, we are able to use these variables in future research to quantify the different types of craniosynostosis. What is Known: • Premature fusion of one or more cranial sutures results in a specific cranial shape. • Clinical diagnosis is relatively simple; however, objective diagnosis based on distinctive values is difficult. What is New: • Using external landmarks and curve analysis, distinctive variables, and values for every type of craniosynostosis related to the specific skull deformities were determined and used to create a diagnostic flowchart for diagnosis. • Validation with an independent data set of 51 patients showed that all patients were correctly classified.

Quantification of Severity of Unilateral Coronal Synostosis.

OBJECTIVES: Severity of unilateral coronal synostosis (UCS) can vary. Quantification is important for treatment, expectations of treatment and natural outcome, and education of the patient and parents. DESIGN: Retrospective study. SETTING: Primary craniofacial center. PATIENTS, PARTICIPANTS: Twenty-three preoperative patients with unilateral coronal craniosynostosis (age < 2 years). INTERVENTION: Utrecht Cranial Shape Quantifier (UCSQ) was used to quantify severity using the variables: asymmetry ratio of frontal peak and ratio of frontal peak gradient. MAIN OUTCOME MEASURES(S): The UCSQ variables were combined and related to visual score using Pearson correlation coefficient; UCSQ and visual score were additionally compared to Di Rocco classification by one-way analysis of variance or Kruskal-Wallis test. All measurements were made on computed tomography scans. RESULTS: Good correlation between UCSQ and visual score was found (r = 0.67). No statistically significant differences were found between group means of UCSQ in the 3 categories of Di Rocco classification (F2,20 = 0.047; P > .05). Kruskal-Wallis test showed no significant differences between group means of visual score in the 3 categories of Di Rocco classification (Kruskal-Wallis H (2) = 0.871; P > .05). CONCLUSIONS: Using UCSQ, we can quantify UCS according to severity using characteristics, it outperforms traditional methods and captures the whole skull shape. In future research, we can apply UCSQ to 3D-photogrammetry due to the utilization of external landmarks.

Automated Classification of Significant Prostate Cancer on MRI: A Systematic Review on the Performance of Machine Learning Applications.

Significant prostate carcinoma (sPCa) classification based on MRI using radiomics or deep learning approaches has gained much interest, due to the potential application in assisting in clinical decision-making. OBJECTIVE: To systematically review the literature (i) to determine which algorithms are most frequently used for sPCa classification, (ii) to investigate whether there exists a relation between the performance and the method or the MRI sequences used, (iii) to assess what study design factors affect the performance on sPCa classification, and (iv) to research whether performance had been evaluated in a clinical setting Methods: The databases Embase and Ovid MEDLINE were searched for studies describing machine learning or deep learning classification methods discriminating between significant and nonsignificant PCa on multiparametric MRI that performed a valid validation procedure. Quality was assessed by the modified radiomics quality score. We computed the median area under the receiver operating curve (AUC) from overall methods and the interquartile range. RESULTS: From 2846 potentially relevant publications, 27 were included. The most frequent algorithms used in the literature for PCa classification are logistic regression (22%) and convolutional neural networks (CNNs) (22%). The median AUC was 0.79 (interquartile range: 0.77-0.87). No significant effect of number of included patients, image sequences, or reference standard on the reported performance was found. Three studies described an external validation and none of the papers described a validation in a prospective clinical trial. CONCLUSIONS: To unlock the promising potential of machine and deep learning approaches, validation studies and clinical prospective studies should be performed with an established protocol to assess the added value in decision-making.

Clinically significant prostate cancer detection and segmentation in low-risk patients using a convolutional neural network on multi-parametric MRI.

OBJECTIVES: To develop an automatic method for identification and segmentation of clinically significant prostate cancer in low-risk patients and to evaluate the performance in a routine clinical setting. METHODS: A consecutive cohort (n = 292) from a prospective database of low-risk patients eligible for the active surveillance was selected. A 3-T multi-parametric MRI at 3 months after inclusion was performed. Histopathology from biopsies was used as reference standard. MRI positivity was defined as PI-RADS score ≥ 3, histopathology positivity was defined as ISUP grade ≥ 2. The selected cohort contained four patient groups: (1) MRI-positive targeted biopsy-positive (n = 116), (2) MRI-negative systematic biopsy-negative (n = 55), (3) MRI-positive targeted biopsy-negative (n = 113), (4) MRI-negative systematic biopsy-positive (n = 8). Group 1 was further divided into three sets and a 3D convolutional neural network was trained using different combinations of these sets. Two MRI sequences (T2w, b = 800 DWI) and the ADC map were used as separate input channels for the model. After training, the model was evaluated on the remaining group 1 patients together with the patients of groups 2 and 3 to identify and segment clinically significant prostate cancer. RESULTS: The average sensitivity achieved was 82-92% at an average specificity of 43-76% with an area under the curve (AUC) of 0.65 to 0.89 for different lesion volumes ranging from > 0.03 to > 0.5 cc. CONCLUSIONS: The proposed deep learning computer-aided method yields promising results in identification and segmentation of clinically significant prostate cancer and in confirming low-risk cancer (ISUP grade ≤ 1) in patients on active surveillance. KEY POINTS: • Clinically significant prostate cancer identification and segmentation on multi-parametric MRI is feasible in low-risk patients using a deep neural network. • The deep neural network for significant prostate cancer localization performs better for lesions with larger volumes sizes (> 0.5 cc) as compared to small lesions (> 0.03 cc). • For the evaluation of automatic prostate cancer segmentation methods in the active surveillance cohort, the large discordance group (MRI positive, targeted biopsy negative) should be included.

Introducing a new method for classifying skull shape abnormalities related to craniosynostosis.

We present a novel technique for classification of skull deformities due to most common craniosynostosis. We included 5 children of every group of the common craniosynostoses (scaphocephaly, brachycephaly, trigonocephaly, and right- and left-sided anterior plagiocephaly) and additionally 5 controls. Our outline-based classification method is described, using the software programs OsiriX, MeVisLab, and Matlab. These programs were used to identify chosen landmarks (porion and exocanthion), create a base plane and a plane at 4 cm, segment outlines, and plot resulting graphs. We measured repeatability and reproducibility, and mean curves of groups were analyzed. All raters achieved excellent intraclass correlation scores (0.994-1.000) and interclass correlation scores (0.989-1.000) for identifying the external landmarks. Controls, scaphocephaly, trigonocephaly, and brachycephaly all have the peak of the forehead in the middle of the curve (180°). In contrary, in anterior plagiocephaly, the peak is shifted (to the left of graph in right-sided and vice versa). Additionally, controls, scaphocephaly, and trigonocephaly have a high peak of the forehead; scaphocephaly has the lowest troughs; in brachycephaly, the width/frontal peak ratio has the highest value with a low frontal peak.Conclusion: We introduced a preliminary study showing an objective and reproducible methodology using CT scans for the analysis of craniosynostosis and potential application of our method to 3D photogrammetry. What is Known: • Diagnosis of craniosynostosis is relatively simple; however, classification of craniosynostosis is difficult and current techniques are not widely applicable. What is New: • We introduce a novel technique for classification of skull deformities due to craniosynostosis, an objective and reproducible methodology using CT scans resulting in characteristic curves. The method is applicable to all 3D-surface rendering techniques. • Using external landmarks and curve analysis, specific and characteristic curves for every type of craniosynostosis related to the specific skull deformities are found.

Feasibility and relevance of discrete vasculature modeling in routine hyperthermia treatment planning.

Purpose: To investigate the effect of patient specific vessel cooling on head and neck hyperthermia treatment planning (HTP). Methods and materials: Twelve patients undergoing radiotherapy were scanned using computed tomography (CT), magnetic resonance imaging (MRI) and contrast enhanced MR angiography (CEMRA). 3D patient models were constructed using the CT and MRI data. The arterial vessel tree was constructed from the MRA images using the 'graph-cut' method, combining information from Frangi vesselness filtering and region growing, and the results were validated against manually placed markers in/outside the vessels. Patient specific HTP was performed and the change in thermal distribution prediction caused by arterial cooling was evaluated by adding discrete vasculature (DIVA) modeling to the Pennes bioheat equation (PBHE). Results: Inclusion of arterial cooling showed a relevant impact, i.e., DIVA modeling predicts a decreased treatment quality by on average 0.19 °C (T90), 0.32 °C (T50) and 0.35 °C (T20) that is robust against variations in the inflow blood rate (|ΔT| < 0.01 °C). In three cases, where the major vessels transverse target volume, notable drops (|ΔT| > 0.5 °C) were observed. Conclusion: Addition of patient-specific DIVA into the thermal modeling can significantly change predicted treatment quality. In cases where clinically detectable vessels pass the heated region, we advise to perform DIVA modeling.

Groupwise Multichannel Image Registration.

Multichannel image registration is an important challenge in medical image analysis. Multichannel images result from modalities such as dual-energy CT or multispectral microscopy. Besides, multichannel feature images can be derived from acquired images, for instance, by applying multiscale feature banks to the original images to register. Multichannel registration techniques have been proposed, but most of them are applicable to only two multichannel images at a time. In the present study, we propose to formulate multichannel registration as a groupwise image registration problem. In this way, we derive a method that allows the registration of two or more multichannel images in a fully symmetric manner (i.e., all images play the same role in the registration procedure), and therefore, has transitive consistency by definition. The method that we introduce is applicable to any number of multichannel images, any number of channels per image, and it allows to take into account correlation between any pair of images and not just corresponding channels. In addition, it is fully modular in terms of dissimilarity measure, transformation model, regularisation method, and optimisation strategy. For two multimodal datasets, we computed feature images from the initially acquired images, and applied the proposed registration technique to the newly created sets of multichannel images. MIND descriptors were used as feature images, and we chose total correlation as groupwise dissimilarity measure. Results show that groupwise multichannel image registration is a competitive alternative to the pairwise multichannel scheme, in terms of registration accuracy and insensitivity towards registration reference spaces.

Automatic tissue segmentation of head and neck MR images for hyperthermia treatment planning.

A hyperthermia treatment requires accurate, patient-specific treatment planning. This planning is based on 3D anatomical models which are generally derived from computed tomography. Because of its superior soft tissue contrast, magnetic resonance imaging (MRI) information can be introduced to improve the quality of these 3D patient models and therefore the treatment planning itself. Thus, we present here an automatic atlas-based segmentation algorithm for MR images of the head and neck. Our method combines multiatlas local weighting fusion with intensity modelling. The accuracy of the method was evaluated using a leave-one-out cross validation experiment over a set of 11 patients for which manual delineation were available. The accuracy of the proposed method was high both in terms of the Dice similarity coefficient (DSC) and the 95th percentile Hausdorff surface distance (HSD) with median DSC higher than 0.8 for all tissues except sclera. For all tissues, except the spine tissues, the accuracy was approaching the interobserver agreement/variability both in terms of DSC and HSD. The positive effect of adding the intensity modelling to the multiatlas fusion decreased when a more accurate atlas fusion method was used.Using the proposed approach we improved the performance of the approach previously presented for H&N hyperthermia treatment planning, making the method suitable for clinical application.

Accurate 3D temperature dosimetry during hyperthermia therapy by combining invasive measurements and patient-specific simulations.

PURPOSE: Dosimetry during deep local hyperthermia treatments in the head and neck currently relies on a limited number of invasively placed temperature sensors. The purpose of this study was to assess the feasibility of 3D dosimetry based on patient-specific temperature simulations and sensory feedback. MATERIALS AND METHODS: The study includes 10 patients with invasive thermometry applied in at least two treatments. Based on their invasive thermometry, we optimised patient-group thermal conductivity and perfusion values for muscle, fat and tumour using a 'leave-one-out' approach. Next, we compared the accuracy of the predicted temperature (ΔT) and the hyperthermia treatment quality (ΔT50) of the optimisations based on the patient-group properties to those based on patient-specific properties, which were optimised using previous treatment measurements. As a robustness check, and to enable comparisons with previous studies, we optimised the parameters not only for an applicator efficiency factor of 40%, but also for 100% efficiency. RESULTS: The accuracy of the predicted temperature (ΔT) improved significantly using patient-specific tissue properties, i.e. 1.0 °C (inter-quartile range (IQR) 0.8 °C) compared to 1.3 °C (IQR 0.7 °C) for patient-group averaged tissue properties for 100% applicator efficiency. A similar accuracy was found for optimisations using an applicator efficiency factor of 40%, indicating the robustness of the optimisation method. Moreover, in eight patients with repeated measurements in the target region, ΔT50 significantly improved, i.e. ΔT50 reduced from 0.9 °C (IQR 0.8 °C) to 0.4 °C (IQR 0.5 °C) using an applicator efficiency factor of 40%. CONCLUSION: This study shows that patient-specific temperature simulations combined with tissue property reconstruction from sensory data provides accurate minimally invasive 3D dosimetry during hyperthermia treatments: T50 in sessions without invasive measurements can be predicted with a median accuracy of 0.4 °C.

Three-dimensional position changes of the midface following Le Fort III advancement in syndromic craniosynostosis.

Little is known about the positional change of the Le Fort III segment following advancement. To study this, pre- and postoperative computed tomography scans of 18 craniosynosthosis patients were analyzed. The Le Fort III segment movement was measured by creating a reference coordinate system and by superpositioning the postoperative over the preoperative scan. On both the pre- and postoperative scans, four anatomical landmarks were marked: the most anterior point of the left and right foramen infraorbitale, the nasion, and the anterior nasal spine. A significant anterior movement of the four reference points was observed. No significant transversal differences were found. A significant difference between the anterior movement of the nasion and anterior nasal spine was found. In vertical dimension, there was a significant cranial movement of nasion in the study group. In addition, from all patients standardized lateral X-rays were viewed to determine the location and direction of force application that were linked to the outcomes of the three-dimensional movement of the nasion and anterior nasal spine (ANS) and the surgical technique. Conclusively, a significant advancement of the midface can be achieved with Le Fort III distraction osteogenesis in this specific patient group. Counterclockwise movement seemed to be the most dominant movement despite different modes of anchorage.

MRI integration into treatment planning of head and neck tumors: Can patient immobilization be avoided?

To assess whether deformable registration between CT and MR images can be used to avoid patient immobilization, we compared registration accuracy in various scenarios, with and without immobilization equipment. Whereas both deformable registration and the use of immobilization equipment improved the registration accuracy, the combination gave the best alignment.

The relevance of MRI for patient modeling in head and neck hyperthermia treatment planning: a comparison of CT and CT-MRI based tissue segmentation on simulated temperature.

PURPOSE: In current clinical practice, head and neck (H&N) hyperthermia treatment planning (HTP) is solely based on computed tomography (CT) images. Magnetic resonance imaging (MRI) provides superior soft-tissue contrast over CT. The purpose of the authors' study is to investigate the relevance of using MRI in addition to CT for patient modeling in H&N HTP. METHODS: CT and MRI scans were acquired for 11 patients in an immobilization mask. Three observers manually segmented on CT, MRI T1 weighted (MRI-T1w), and MRI T2 weighted (MRI-T2w) images the following thermo-sensitive tissues: cerebrum, cerebellum, brainstem, myelum, sclera, lens, vitreous humor, and the optical nerve. For these tissues that are used for patient modeling in H&N HTP, the interobserver variation of manual tissue segmentation in CT and MRI was quantified with the mean surface distance (MSD). Next, the authors compared the impact of CT and CT and MRI based patient models on the predicted temperatures. For each tissue, the modality was selected that led to the lowest observer variation and inserted this in the combined CT and MRI based patient model (CT and MRI), after a deformable image registration. In addition, a patient model with a detailed segmentation of brain tissues (including white matter, gray matter, and cerebrospinal fluid) was created (CT and MRIdb). To quantify the relevance of MRI based segmentation for H&N HTP, the authors compared the predicted maximum temperatures in the segmented tissues (Tmax) and the corresponding specific absorption rate (SAR) of the patient models based on (1) CT, (2) CT and MRI, and (3) CT and MRIdb. RESULTS: In MRI, a similar or reduced interobserver variation was found compared to CT (maximum of median MSD in CT: 0.93 mm, MRI-T1w: 0.72 mm, MRI-T2w: 0.66 mm). Only for the optical nerve the interobserver variation is significantly lower in CT compared to MRI (median MSD in CT: 0.58 mm, MRI-T1w: 1.27 mm, MRI-T2w: 1.40 mm). Patient models based on CT (Tmax: 38.0 °C) and CT and MRI (Tmax: 38.1 °C) result in similar simulated temperatures, while CT and MRIdb (Tmax: 38.5 °C) resulted in significantly higher temperatures. The SAR corresponding to these temperatures did not differ significantly. CONCLUSIONS: Although MR imaging reduces the interobserver variation in most tissues, it does not affect simulated local tissue temperatures. However, the improved soft-tissue contrast provided by MRI allows generating a detailed brain segmentation, which has a strong impact on the predicted local temperatures and hence may improve simulation guided hyperthermia.

Quantification of heterogeneity as a biomarker in tumor imaging: a systematic review.

BACKGROUND: Many techniques are proposed for the quantification of tumor heterogeneity as an imaging biomarker for differentiation between tumor types, tumor grading, response monitoring and outcome prediction. However, in clinical practice these methods are barely used. This study evaluates the reported performance of the described methods and identifies barriers to their implementation in clinical practice. METHODOLOGY: The Ovid, Embase, and Cochrane Central databases were searched up to 20 September 2013. Heterogeneity analysis methods were classified into four categories, i.e., non-spatial methods (NSM), spatial grey level methods (SGLM), fractal analysis (FA) methods, and filters and transforms (F&T). The performance of the different methods was compared. PRINCIPAL FINDINGS: Of the 7351 potentially relevant publications, 209 were included. Of these studies, 58% reported the use of NSM, 49% SGLM, 10% FA, and 28% F&T. Differentiation between tumor types, tumor grading and/or outcome prediction was the goal in 87% of the studies. Overall, the reported area under the curve (AUC) ranged from 0.5 to 1 (median 0.87). No relation was found between the performance and the quantification methods used, or between the performance and the imaging modality. A negative correlation was found between the tumor-feature ratio and the AUC, which is presumably caused by overfitting in small datasets. Cross-validation was reported in 63% of the classification studies. Retrospective analyses were conducted in 57% of the studies without a clear description. CONCLUSIONS: In a research setting, heterogeneity quantification methods can differentiate between tumor types, grade tumors, and predict outcome and monitor treatment effects. To translate these methods to clinical practice, more prospective studies are required that use external datasets for validation: these datasets should be made available to the community to facilitate the development of new and improved methods.

Temperature simulations in hyperthermia treatment planning of the head and neck region: rigorous optimization of tissue properties.

BACKGROUND AND PURPOSE: Hyperthermia treatment planning (HTP) is used in the head and neck region (H&N) for pretreatment optimization, decision making, and real-time HTP-guided adaptive application of hyperthermia. In current clinical practice, HTP is based on power-absorption predictions, but thermal dose-effect relationships advocate its extension to temperature predictions. Exploitation of temperature simulations requires region- and temperature-specific thermal tissue properties due to the strong thermoregulatory response of H&N tissues. The purpose of our work was to develop a technique for patient group-specific optimization of thermal tissue properties based on invasively measured temperatures, and to evaluate the accuracy achievable. PATIENTS AND METHODS: Data from 17 treated patients were used to optimize the perfusion and thermal conductivity values for the Pennes bioheat equation-based thermal model. A leave-one-out approach was applied to accurately assess the difference between measured and simulated temperature (∆T). The improvement in ∆T for optimized thermal property values was assessed by comparison with the ∆T for values from the literature, i.e., baseline and under thermal stress. RESULTS: The optimized perfusion and conductivity values of tumor, muscle, and fat led to an improvement in simulation accuracy (∆T: 2.1 ± 1.2 °C) compared with the accuracy for baseline (∆T: 12.7 ± 11.1 °C) or thermal stress (∆T: 4.4 ± 3.5 °C) property values. CONCLUSION: The presented technique leads to patient group-specific temperature property values that effectively improve simulation accuracy for the challenging H&N region, thereby making simulations an elegant addition to invasive measurements. The rigorous leave-one-out assessment indicates that improvements in accuracy are required to rely only on temperature-based HTP in the clinic.

Feasibility of multimodal deformable registration for head and neck tumor treatment planning.

PURPOSE: To investigate the feasibility of using deformable registration in clinical practice to fuse MR and CT images of the head and neck for treatment planning. METHOD AND MATERIALS: A state-of-the-art deformable registration algorithm was optimized, evaluated, and compared with rigid registration. The evaluation was based on manually annotated anatomic landmarks and regions of interest in both modalities. We also developed a multiparametric registration approach, which simultaneously aligns T1- and T2-weighted MR sequences to CT. This was evaluated and compared with single-parametric approaches. RESULTS: Our results show that deformable registration yielded a better accuracy than rigid registration, without introducing unrealistic deformations. For deformable registration, an average landmark alignment of approximatively 1.7 mm was obtained. For all the regions of interest excluding the cerebellum and the parotids, deformable registration provided a median modified Hausdorff distance of approximatively 1 mm. Similar accuracies were obtained for the single-parameter and multiparameter approaches. CONCLUSIONS: This study demonstrates that deformable registration of head-and-neck CT and MR images is feasible, with overall a significanlty higher accuracy than for rigid registration.

CT-based patient modeling for head and neck hyperthermia treatment planning: manual versus automatic normal-tissue-segmentation.

BACKGROUND AND PURPOSE: Clinical trials have shown that hyperthermia, as adjuvant to radiotherapy and/or chemotherapy, improves treatment of patients with locally advanced or recurrent head and neck (H&N) carcinoma. Hyperthermia treatment planning (HTP) guided H&N hyperthermia is being investigated, which requires patient specific 3D patient models derived from Computed Tomography (CT)-images. To decide whether a recently developed automatic-segmentation algorithm can be introduced in the clinic, we compared the impact of manual- and automatic normal-tissue-segmentation variations on HTP quality. MATERIAL AND METHODS: CT images of seven patients were segmented automatically and manually by four observers, to study inter-observer and intra-observer geometrical variation. To determine the impact of this variation on HTP quality, HTP was performed using the automatic and manual segmentation of each observer, for each patient. This impact was compared to other sources of patient model uncertainties, i.e. varying gridsizes and dielectric tissue properties. RESULTS: Despite geometrical variations, manual and automatic generated 3D patient models resulted in an equal, i.e. 1%, variation in HTP quality. This variation was minor with respect to the total of other sources of patient model uncertainties, i.e. 11.7%. CONCLUSIONS: Automatically generated 3D patient models can be introduced in the clinic for H&N HTP.