A concept for holistic whole body MRI data analysis, Imiomics.

PURPOSE: To present and evaluate a whole-body image analysis concept, Imiomics (imaging-omics) and an image registration method that enables Imiomics analyses by deforming all image data to a common coordinate system, so that the information in each voxel can be compared between persons or within a person over time and integrated with non-imaging data. METHODS: The presented image registration method utilizes relative elasticity constraints of different tissue obtained from whole-body water-fat MRI. The registration method is evaluated by inverse consistency and Dice coefficients and the Imiomics concept is evaluated by example analyses of importance for metabolic research using non-imaging parameters where we know what to expect. The example analyses include whole body imaging atlas creation, anomaly detection, and cross-sectional and longitudinal analysis. RESULTS: The image registration method evaluation on 128 subjects shows low inverse consistency errors and high Dice coefficients. Also, the statistical atlas with fat content intensity values shows low standard deviation values, indicating successful deformations to the common coordinate system. The example analyses show expected associations and correlations which agree with explicit measurements, and thereby illustrate the usefulness of the proposed Imiomics concept. CONCLUSIONS: The registration method is well-suited for Imiomics analyses, which enable analyses of relationships to non-imaging data, e.g. clinical data, in new types of holistic targeted and untargeted big-data analysis.

Use of a Mobile Intraoperative Computed Tomography Scanner for Navigation Registration During Laser Interstitial Thermal Therapy of Brain Tumors.

OBJECTIVE: In recent years laser interstitial thermal therapy (LITT) has become the ablative neurosurgical procedure of choice. Multiple methods for registration and laser fiber verification have been described, with each method requiring multiple steps and significant time expenditure. We evaluated the use of a commercially available mobile computed tomography (CT) scanner for stereotactic registration during LITT for brain tumors in an attempt to simplify the procedure and improve intraoperative awareness of laser position. METHODS: This is a retrospective chart review comparing LITT of brain tumors in 23 patients undergoing a standard protocol requiring skull pins and transport of the patient to a CT suite to obtain a reference scan compared with 14 patients in whom the Medtronic O-arm was used intraoperatively for navigation registration and confirmation of laser position. RESULTS: Total ablation of the target was achieved in all patients with no surgical complications. Total surgery time was shorter for the O-arm group than for the standard protocol group, once experience was gained with bringing the O-arm in and out of the surgical field. Return from the magnetic resonance imaging suite to the operating room for repositioning of the laser was required for 1 patient in the standard protocol group, but for no patients in the O-arm group. Once experience was gained with using the O-arm, estimated surgical costs were lower for this group. CONCLUSIONS: Use of a mobile intraoperative CT scanner for navigation registration and confirmation of laser position during LITT may play a role in streamlining the procedure and improving patient safety and comfort.

Evaluation of a spectral subtraction strategy to suppress reverberant energy in cochlear implant devices.

The smearing effects of room reverberation can significantly impair the ability of cochlear implant (CI) listeners to understand speech. To ameliorate the effects of reverberation, current dereverberation algorithms focus on recovering the direct sound from the reverberated signal by inverse filtering the reverberation process. This contribution describes and evaluates a spectral subtraction (SS) strategy capable of suppressing late reflections. Late reflections are the most detrimental to speech intelligibility by CI listeners as reverberation increases. By tackling only the late part of reflections, it is shown that users of CI devices can benefit from the proposed strategy even in highly reverberant rooms. The proposed strategy is also compared against an ideal reverberant (binary) masking approach. Speech intelligibility results indicate that the proposed SS solution is able to suppress additive reverberant energy to a degree comparable to that achieved by an ideal binary mask. The added advantage is that the SS strategy proposed in this work can allow for a potentially real-time implementation in clinical CI processors.

Quantitative susceptibility mapping of the motor cortex in amyotrophic lateral sclerosis and primary lateral sclerosis.

OBJECTIVE: The diagnosis of amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS) is often difficult because of a lack of disease biomarkers. The purpose of this study was to investigate quantitative susceptibility mapping (QSM) of the motor cortex as a potential quantitative biomarker for the diagnosis of ALS and PLS. MATERIALS AND METHODS: From a retrospective database, QSM images of 16 patients with upper motor neuron disease (nine men [56%], seven women; mean age, 56.3 years; 12 with ALS, four with PLS) and 23 control patients (13 men [56%], 10 women; mean age, 56.6 years) were reviewed. Two neuroradiologists, blinded to diagnosis, qualitatively assessed QSM, T2- and T2*-weighted, and T2-weighted FLAIR images. Relative motor cortex susceptibility was calculated by subtraction of adjacent white matter and CSF signal intensity from mean motor cortex susceptibility on the axial image most representative of the right- or left-hand lobule, and ROC analysis was performed. The Fisher exact and Student t tests were used to evaluate for statistical differences between the groups. RESULTS: Qualitatively, QSM had greater diagnostic accuracy than T2-weighted, T2*-weighted, or T2-weighted FLAIR imaging for the diagnosis of ALS and PLS. Quantitatively, relative motor cortex susceptibility was found to be significantly greater in patients with motor neuron disease than in control patients (46.0 and 35.0 ppb; p < 0.001). ROC analysis showed an AUC of 0.88 (p < 0.0001) and an optimal cutoff value of 40.5 ppb for differentiating control patients from patients with ALS or PLS (sensitivity, 87.5%; specificity, 87.0%). CONCLUSION: QSM is a sensitive and specific quantitative biomarker of iron deposition in the motor cortex in ALS and PLS.

The 4D hyperspherical diffusion wavelet: A new method for the detection of localized anatomical variation.

Recently, the HyperSPHARM algorithm was proposed to parameterize multiple disjoint objects in a holistic manner using the 4D hyperspherical harmonics. The HyperSPHARM coefficients are global; they cannot be used to directly infer localized variations in signal. In this paper, we present a unified wavelet framework that links Hyper-SPHARM to the diffusion wavelet transform. Specifically, we will show that the HyperSPHARM basis forms a subset of a wavelet-based multiscale representation of surface-based signals. This wavelet, termed the hyperspherical diffusion wavelet, is a consequence of the equivalence of isotropic heat diffusion smoothing and the diffusion wavelet transform on the hypersphere. Our framework allows for the statistical inference of highly localized anatomical changes, which we demonstrate in the first-ever developmental study on the hyoid bone investigating gender and age effects. We also show that the hyperspherical wavelet successfully picks up group-wise differences that are barely detectable using SPHARM.

Automatic method for thalamus parcellation using multi-modal feature classification.

Segmentation and parcellation of the thalamus is an important step in providing volumetric assessment of the impact of disease n brain structures. Conventionally, segmentation is carried out on T1-weighted magnetic resonance (MR) images and nuclear parcellation using diffusion weighted MR images. We present the first fully automatic method that incorporates both tissue contrasts and several derived fea-fractional anisotrophy, fiber orientation from the 5D Knutsson representation of the principal eigenvectors, and connectivity between the thalamus and the cortical lobes, as features. Combining these multiple information sources allows us to identify discriminating dimensions and thus parcellate the thalamic nuclei. A hierarchical random forest framework with a multidimensional feature per voxel, first distinguishes thalamus from background, and then separates each group of thalamic nuclei. Using a leave one out cross-validation on 12 subjects we have a mean Dice score of 0.805 and 0.799 for the left and right thalami, respectively. We also report overlap for the thalamic nuclear groups.

The role of glass ionomer cement on the remineralization of infected dentin: an in vivo study.

PURPOSE: This study's purpose was to investigate the effect of a glass ionomer cement as a liner over infected unexcavated dentin after 60 days and at 10 to 15 months. METHODS: Forty-five permanent molars with deep carious lesions were selected. Fragments of carious dentin were removed prior to lining the cavity (baseline sample) with glass ionomer cement (G1) or an inert wax material (G2). Cavities were restored with composite resin and reopened 60 days later, when other fragments were removed (60-day sample). The dentin morphology (scanning electron microscopy) and mineral content of calcium, phosphorus, and fluorine were assessed. During the follow-up periods (60 days and 10 to 15 months), restorations were evaluated and standardized radiographs were taken. A postprocessing routine was used to identify changes in the radiographic density between periods. RESULTS: After 60 days, the dentin exhibited a better organization, fewer bacteria, and signs of remineralization. The weight percents of calcium and phosphorus were higher 60 days after the cavity sealing, regardless of the group. Higher gray levels of carious and sound dentin were seen on the 10- to 15-month radiographs, irrespective of the group. The success rates of G1 and G2 were 89 percent and 88 percent, respectively. CONCLUSIONS: The lining material isn't fundamental for caries arrestment. Early (60-day) and late (10 to 15 months) dentin changes occurred, indicating the remineralization of dentin carious tissue.

Visualizing Cardiovascular Magnetic Resonance (CMR) imagery: challenges and opportunities.

Cardiovascular Magnetic Resonance (CMR) imaging is an essential technique for measuring regional myocardial function. However, it is a time-consuming and cognitively demanding task to interpret, identify and compare various motion characteristics based on watching CMR imagery. In this work, we focus on the problems of visualising imagery resulting from 2D myocardial tagging in CMR. In particular we provide an overview of the current state of the art of relevant visualization techniques, and a discussion on why the problem is difficult from a perceptual perspective. Finally, we introduce a proof-of-concept multilayered visualization user interface for visualizing CMR data using multiple derived attributes encoded into multivariate glyphs. An initial evaluation of the system by clinicians suggested a great potential for this visualisation technology to become a clinical practice in the future.

Identification of differentially-expressed genes potentially implicated in drought response in pitaya (Hylocereus undatus) by suppression subtractive hybridization and cDNA microarray analysis.

Drought is one of the most severe threats to the growth, development and yield of plant. In order to unravel the molecular basis underlying the high tolerance of pitaya (Hylocereus undatus) to drought stress, suppression subtractive hybridization (SSH) and cDNA microarray approaches were firstly combined to identify the potential important or novel genes involved in the plant responses to drought stress. The forward (drought over drought-free) and reverse (drought-free over drought) suppression subtractive cDNA libraries were constructed using in vitro shoots of cultivar 'Zihonglong' exposed to drought stress and drought-free (control). A total of 2112 clones, among which half were from either forward or reverse SSH library, were randomly picked up to construct a pitaya cDNA microarray. Microarray analysis was carried out to verify the expression fluctuations of this set of clones upon drought treatment compared with the controls. A total of 309 expressed sequence tags (ESTs), 153 from forward library and 156 from reverse library, were obtained, and 138 unique ESTs were identified after sequencing by clustering and blast analyses, which included genes that had been previously reported as responsive to water stress as well as some functionally unknown genes. Thirty six genes were mapped to 47 KEGG pathways, including carbohydrate metabolism, lipid metabolism, energy metabolism, nucleotide metabolism, and amino acid metabolism of pitaya. Expression analysis of the selected ESTs by reverse transcriptase polymerase chain reaction (RT-PCR) corroborated the results of differential screening. Moreover, time-course expression patterns of these selected ESTs further confirmed that they were closely responsive to drought treatment. Among the differentially expressed genes (DEGs), many are related to stress tolerances including drought tolerance. Thereby, the mechanism of drought tolerance of this pitaya genotype is a very complex physiological and biochemical process, in which multiple metabolism pathways and many genes were implicated. The data gained herein provide an insight into the mechanism underlying the drought stress tolerance of pitaya, as well as may facilitate the screening of candidate genes for drought tolerance.

Analysis of cochlear implant artifact removal techniques using the continuous wavelet transform.

When patients with cochlear implants (CI) undergo cortical auditory evoked potential (CAEP) tests to evaluate their hearing, a large electrical artifact introduced by the CI obscures the relevant information in the signal. Several methods have been developed for the purpose of removing the CI artifact; however, there is no gold standard (i.e., patient's auditory response before the CI) to assess the effectiveness of these methods in terms of successful removal of artifact. To address this crucial shortcoming, we employ time-frequency (TF) signal representation (i.e., continuous wavelet transform (CWT)) to evaluate the effectiveness of two recent CI removal techniques, known as the subtraction and polynomial methods. Our results show that polynomial method consistently outperforms the subtraction method in the presence of tone stimulus. These results also indicate a possible CWT-based method for removing the CI artifact from a speech stimuli response, which the subtraction and polynomial methods cannot do.

Mobile Health (mHealth) biomedical imaging paradigm.

Technology assisted methods for medical diagnosis and biomedical health monitoring are rapidly shifting from classical invasive methods to handheld-based non-invasive approaches. Biomedical imagining is one of the most prominent practices of non-invasive mechanisms in medical applications. This paper considers the medical imaging schemes for Mobile Health (mHealth) applications and studies the feasibility of future mobile systems for accommodating image informatics capabilities.

[Proteomics and personalized medicine]. / Proteomica e medicina personalizzata.

With the disclosure of the human genome a new era for bio-medicine has arisen, characterized by the challenge to investigate pathogenic mechanisms, studying simultaneously metabolites, DNA, RNA, and proteins. As a result, the "omics" revolution boomed, giving birth to a new medicine named "omics-based medicine". Among the other "omics", proteomics has been widely used in medicine, since it can produce a more "holistic" overview of a disease and provide a "constellation" of possible specific markers, a molecular fingerprinting that defines the clinical condition of an individual. Endpoint of this comprehensive and detailed analysis is the "diagnostic-omics", i.e. the achievement of personalized diagnoses with obvious benefits for prevention and therapy and this goal can be reached only with a perfect integration between clinicians and proteomists. To impact on the possible key factors involved in the pathological processes, oligonucleotide-based knock-down strategies can be helpful. They exploit omics-derived molecular tools (antisense, siRNA, ribozymes, decoys, and aptamers) that can be used to inhibit, at transcriptional or post-transcriptional levels, the events leading to protein synthesis, thus decreasing its expression. The identification of the pivotal mechanisms involved in diseases using global, "scenic" approaches such as the "omics" ones, and the subsequent validation and detailed description of the processes by specific molecular tools, can result in a more preventive, predictive and personalized medicine.

Multimodal imaging of tumor response to sorafenib combined with radiation therapy: comparison between diffusion-weighted MRI, choline spectroscopy and 18F-FLT PET imaging.

The purpose of this study was to determine the value of different imaging modalities, that is, magnetic resonance imaging/spectroscopy (MRI/MRS) and positron emission tomography (PET), to assess early tumor response to sorafenib with or without radiotherapy. Diffusion-weighted (DW)-MRI, choline (1)H MRS at 11.7 T, and (18)F-FLT PET imaging were used to image fibrosarcoma (FSaII) tumor-bearing mice over time. The imaging markers were compared with apoptosis cell death and cell proliferation measurements assessed by histology. Anti-proliferative effects of sorafenib were evidenced by (1)H MRS and (18)F-FLT PET after 2 days of treatment with sorafenib, with no additional effect of the combination with radiation therapy, results that are in agreement with Ki67 staining. Apparent diffusion coefficient calculated using DW-MRI was not modified after 2 days of treatment with sorafenib, but showed significant increase 24 h after 2 days of sorafenib treatment combined with consecutive irradiation. The three imaging markers were able to show early tumor response as soon as 24 h after treatment initiation, with choline MRS and (18)F-FLT being sensitive to sorafenib in monotherapy as well as in combined therapy with irradiation, whereas DW-MRI was only sensitive to the combination of sorafenib with radiotherapy.

Joint CT/CBCT deformable registration and CBCT enhancement for cancer radiotherapy.

This paper details an algorithm to simultaneously perform registration of computed tomography (CT) and cone-beam computed (CBCT) images, and image enhancement of CBCT. The algorithm employs a viscous fluid model which naturally incorporates two components: a similarity measure for registration and an intensity correction term for image enhancement. Incorporating an intensity correction term improves the registration results. Furthermore, applying the image enhancement term to CBCT imagery leads to an intensity corrected CBCT with better image quality. To achieve minimal processing time, the algorithm is implemented on a graphic processing unit (GPU) platform. The advantage of the simultaneous optimization strategy is quantitatively validated and discussed using a synthetic example. The effectiveness of the proposed algorithm is then illustrated using six patient datasets, three head-and-neck datasets and three prostate datasets.

Registration of a validated mechanical atlas of middle ear for surgical simulation.

This paper is centered on the development of a new training and rehearsal simulation system for middle ear surgery. First, we have developed and validated a mechanical atlas based on finite element method of the human middle ear. The atlas is based on a microMRI. Its mechanical behavior computed in real-time has been successfully validated. In addition, we propose a method for the registration of the mechanical atlas on patient imagery. The simulation can be used for a rehearsal surgery with the geometrical anatomy of a given patient and with mechanical data that are validated. Moreover, this process does not necessitate a complete re-built of the model.

Subtraction artifacts and frequency (mis-)alignment in J-difference GABA editing.

PURPOSE: To compare the repeatability of γ-aminobutyric acid (GABA) measurements using J-difference editing, before and after spectral realignment-a technique which has previously been demonstrated to improve the quality of J-difference GABA spectra. MATERIALS AND METHODS: We performed in vivo measurements in three brain regions (occipital, sensorimotor, and dorsolateral prefrontal cortex [DLPFC]), and analyzed these using alternative alignment approaches to evaluate the impact of alignment on repeatability: "Independent alignment" (aligning each subspectrum independently) and "Pairwise alignment" (aligning each on and off subspectrum as a pair) were compared. RESULTS: Pairwise alignment improved the group mean coefficient of variation in all regions; 0.4% in occipital, 1.1% in sensorimotor, and 1.1% in DLPFC. Independent alignment resulted in subtraction artifacts in the majority of cases, and increased the coefficient of variation in the DLPFC by 9.4%. Simulations demonstrate that the GABA quantification error in datasets with high B0 drift, is 4.5% without alignment, but <1% with optimal alignment. CONCLUSION: Pairwise alignment improves the repeatability of GABA spectroscopy data. However, independently aligning all on and off subspectra can lead to artifacts and worse repeatability when compared with nonaligned data.

Implementation and evaluation of an expectation maximization reconstruction algorithm for gamma emission breast tomosynthesis.

PURPOSE: We are developing a dual modality tomosynthesis breast scanner in which x-ray transmission tomosynthesis and gamma emission tomosynthesis are performed sequentially with the breast in a common configuration. In both modalities projection data are obtained over an angular range of less than 180° from one side of the mildly compressed breast resulting in incomplete and asymmetrical sampling. The objective of this work is to implement and evaluate a maximum likelihood expectation maximization (MLEM) reconstruction algorithm for gamma emission breast tomosynthesis (GEBT). METHODS: A combination of Monte Carlo simulations and phantom experiments was used to test the MLEM algorithm for GEBT. The algorithm utilizes prior information obtained from the x-ray breast tomosynthesis scan to partially compensate for the incomplete angular sampling and to perform attenuation correction (AC) and resolution recovery (RR). System spatial resolution, image artifacts, lesion contrast, and signal to noise ratio (SNR) were measured as image quality figures of merit. To test the robustness of the reconstruction algorithm and to assess the relative impacts of correction techniques with changing angular range, simulations and experiments were both performed using acquisition angular ranges of 45°, 90° and 135°. For comparison, a single projection containing the same total number of counts as the full GEBT scan was also obtained to simulate planar breast scintigraphy. RESULTS: The in-plane spatial resolution of the reconstructed GEBT images is independent of source position within the reconstructed volume and independent of acquisition angular range. For 45° acquisitions, spatial resolution in the depth dimension (the direction of breast compression) is degraded with increasing source depth (increasing distance from the collimator surface). Increasing the acquisition angular range from 45° to 135° both greatly reduces this depth dependence and improves the average depth dimension resolution from 10.8 to 4.8 mm. The 135° acquisition results in a near-isotropic, spatially uniform 3D resolution of approximately 4.3 mm full width at half maximum. Background nonuniformity (cupping) artifacts arise primarily from angular incompleteness for small angular range acquisition but primarily from gamma ray attenuation at larger angular range. However, background artifacts can be largely eliminated if both prior information regularization and AC are applied. An artificial decrease in lesion voxel value with increasing lesion depth can also be substantially reduced through a combination of AC and RR. In experiments using compressible gelatin breast phantoms, lesion contrast and SNR are about 2.6-8.8 times and 2.3-5.6 times higher, respectively, in GEBT than in planar breast scintigraphy depending on the acquisition angle, the gamma camera trajectory, and the lesion location. In addition, the strong reduction in lesion contrast and SNR with increasing lesion depth that is observed in planar breast scintigraphy can be largely overcome in GEBT. CONCLUSIONS: The authors have demonstrated a promising EM-based reconstruction scheme for use in GEBT. Compared to planar breast scintigraphy GEBT provides superior and less position-dependent lesion contrast, lesion SNR, and spatial resolution as well as more accurate quantification of lesion-to-background activity concentration ratio.

Fluorescence excitation analysis by two-photon confocal laser scanning microscopy: a new method to identify fluorescent nanoparticles on histological tissue sections.

In the present study, we make use of the ability of two-photon confocal laser scanning microscopes (CLSMs) equipped with tunable lasers to produce spectral excitation image sequences. Furthermore, unmixing, which is usually performed on emission image sequences, is performed on these excitation image sequences. We use factor analysis of medical image sequences (FAMIS), which produces factor images, to unmix spectral image sequences of stained structures in tissue sections to provide images of characterized stained cellular structures. This new approach is applied to histological tissue sections of mouse aorta containing labeled iron nanoparticles stained with Texas Red and counterstained with SYTO13, to obtain visual information about the accumulation of these nanoparticles in the arterial wall. The possible presence of Texas Red is determined using a two-photon CLSM associated with FAMIS via the excitation spectra. Texas Red and SYTO13 are thus differentiated, and corresponding factor images specify their possible presence and cellular localization. In conclusion, the designed protocol shows that sequences of images obtained by excitation in a two-photon CLSM enables characterization of Texas Red-stained nanoparticles and other markers. This methodology offers an alternative and complementary solution to the conventional use of emission spectra unmixing to localize fluorescent nanoparticles in tissue samples.

Azithromycin as an adjunctive treatment of aggressive periodontitis: radiographic findings of a 12-month randomized clinical trial.

PURPOSE: To compare the 12-month radiographic outcomes following the use of azithromycin or placebo as adjuncts to non-surgical periodontal treatment of AgP. METHODS: 17 aggressive periodontitis (AgP) subjects 13-26 years old were randomly assigned to receive scaling and root planing (SRP) with systemic azithromycin or placebo. Standardized radiographs were taken at baseline and 12 months postoperatively. Recall visits consisting of oral prophylaxis and oral hygiene instructions were performed during the 12 months. Digital image subtraction analysis and linear bone measurements were conducted by a blinded and calibrated examiner. Student t-tests were used for within and between-groups comparisons. ANCOVA was applied for between-group comparisons of changes in linear bone level adjusting for baseline values. RESULTS: There were significant gains in linear bone levels in the azithromycin (0.55 +/- 0.10 mm) and placebo (0.42 +/- 0.07 mm) groups between the baseline and 12-month postoperative visits. There were also significant gains in bone density in the two treatment groups. No significant differences were observed between the two treatments in the amount of linear bone gain or bone density during the follow-up period. The use of azithromycin as an adjunct to SRP in the treatment of AgP did not result in significant radiographic bone level changes compared to placebo.

Data mining framework for fatty liver disease classification in ultrasound: a hybrid feature extraction paradigm.

PURPOSE: Fatty liver disease (FLD) is an increasing prevalent disease that can be reversed if detected early. Ultrasound is the safest and ubiquitous method for identifying FLD. Since expert sonographers are required to accurately interpret the liver ultrasound images, lack of the same will result in interobserver variability. For more objective interpretation, high accuracy, and quick second opinions, computer aided diagnostic (CAD) techniques may be exploited. The purpose of this work is to develop one such CAD technique for accurate classification of normal livers and abnormal livers affected by FLD. METHODS: In this paper, the authors present a CAD technique (called Symtosis) that uses a novel combination of significant features based on the texture, wavelet transform, and higher order spectra of the liver ultrasound images in various supervised learning-based classifiers in order to determine parameters that classify normal and FLD-affected abnormal livers. RESULTS: On evaluating the proposed technique on a database of 58 abnormal and 42 normal liver ultrasound images, the authors were able to achieve a high classification accuracy of 93.3% using the decision tree classifier. CONCLUSIONS: This high accuracy added to the completely automated classification procedure makes the authors' proposed technique highly suitable for clinical deployment and usage.