Publications

2016
Zhang F, Song Y, Cai W, Hauptmann AG, Liu S, Pujol S, Kikinis R, Fulham MJ, Feng DD, Chen M. Dictionary Pruning with Visual Word Significance for Medical Image Retrieval. Neurocomputing. 2016;177 :75-88.Abstract
Content-based medical image retrieval (CBMIR) is an active research area for disease diagnosis and treatment but it can be problematic given the small visual variations between anatomical structures. We propose a retrieval method based on a bag-of-visual-words (BoVW) to identify discriminative characteristics between different medical images with Pruned Dictionary based on Latent Semantic Topic description. We refer to this as the PD-LST retrieval. Our method has two main components. First, we calculate a topic-word significance value for each visual word given a certain latent topic to evaluate how the word is connected to this latent topic. The latent topics are learnt, based on the relationship between the images and words, and are employed to bridge the gap between low-level visual features and high-level semantics. These latent topics describe the images and words semantically and can thus facilitate more meaningful comparisons between the words. Second, we compute an overall-word significance value to evaluate the significance of a visual word within the entire dictionary. We designed an iterative ranking method to measure overall-word significance by considering the relationship between all latent topics and words. The words with higher values are considered meaningful with more significant discriminative power in differentiating medical images. We evaluated our method on two public medical imaging datasets and it showed improved retrieval accuracy and efficiency.
Santillo AF, Lundblad K, Nilsson M, Landqvist Waldö M, van Westen D, Lätt J, Blennow Nordström E, Vestberg S, Lindberg O, Nilsson C. Grey and White Matter Clinico-Anatomical Correlates of Disinhibition in Neurodegenerative Disease. PLoS One. 2016;11 (10) :e0164122.Abstract
Disinhibition is an important symptom in neurodegenerative diseases. However, the clinico-anatomical underpinnings remain controversial. We explored the anatomical correlates of disinhibition in neurodegenerative disease using the perspective of grey and white matter imaging. Disinhibition was assessed with a neuropsychological test and a caregiver information-based clinical rating scale in 21 patients with prefrontal syndromes due to behavioural variant frontotemporal dementia (n = 12) or progressive supranuclear palsy (n = 9), and healthy controls (n = 25). Cortical thickness was assessed using the Freesurfer software on 3T MRI data. The integrity of selected white matter tracts was determined by the fractional anisotropy (FA) from Diffusion Tensor Imaging. Disinhibition correlated with the cortical thickness of the right parahippocampal gyrus, right orbitofrontal cortex and right insula and the FA of the right uncinate fasciculus and right anterior cingulum. Notably, no relationship was seen with the thickness of ventromedial prefrontal cortex. Our results support an associative model of inhibitory control, distributed in a medial temporal lobe-insular-orbitofrontal network, connected by the intercommunicating white matter tracts. This reconciles some of the divergences among previous studies, but also questions the current conceptualisation of the "prefrontal" syndrome and the central role attributed to the ventromedial prefrontal cortex in inhibitory control.
Royuela-Del-Val J, Cordero-Grande L, Simmross-Wattenberg F, Martín-Fernández M, Alberola-López C. Nonrigid groupwise registration for motion estimation and compensation in compressed sensing reconstruction of breath-hold cardiac cine MRI. Magn Reson Med. 2016;75 (4) :1525-36.Abstract
PURPOSE: Compressed sensing methods with motion estimation and compensation techniques have been proposed for the reconstruction of accelerated dynamic MRI. However, artifacts that naturally arise in compressed sensing reconstruction procedures hinder the estimation of motion from reconstructed images, especially at high acceleration factors. This work introduces a robust groupwise nonrigid motion estimation technique applied to the compressed sensing reconstruction of dynamic cardiac cine MRI sequences. THEORY AND METHODS: A spatio-temporal regularized, groupwise, nonrigid registration method based on a B-splines deformation model and a least squares metric is used to estimate and to compensate the movement of the heart in breath-hold cine acquisitions and to obtain a quasistatic sequence with highly sparse representation in temporally transformed domains. RESULTS: Short axis in vivo datasets are used for validation, both original multicoil as well as DICOM data. Fully sampled data were retrospectively undersampled with various acceleration factors and reconstructions were compared with the two well-known methods k-t FOCUSS and MASTeR. The proposed method achieves higher signal to error ratio and structure similarity index for medium to high acceleration factors. CONCLUSIONS: Reconstruction methods based on groupwise registration show higher quality reconstructions for cardiac cine images than the pairwise counterparts tested.
Algotsson J, Forsman J, Topgaard D, Söderman O. Electrostatic interactions are important for the distribution of Gd(DTPA)(2-) in articular cartilage. Magn Reson Med. 2016;76 (2) :500-9.Abstract
PURPOSE: The delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) method can be used to assess the content of glycosaminoglycan in cartilage. In in vitro and model studies, the content of glycosaminoglycan is often expressed in terms of a fixed charge density (FCD). Values of the fixed charge density obtained using the dGEMRIC method differs from values obtained using other methods. The purpose of this work was to further clarify the origin of this discrepancy. METHODS: dGEMRIC experiments were performed in a μMRI setup on a custom-designed, well-defined model system capturing the relevant ionic features of cartilage. The model system allows for good control over and systematic variation of relevant parameters. The experimental data was compared with results from Monte Carlo simulations on a coarse-grained model. RESULTS: Application of ideal Donnan theory on data obtained from experiments as well as simulations lead to underestimation of the fixed charge density, in agreement with previous studies. CONCLUSION: To obtain more accurate estimates of the fixed charge density using the dGEMRIC method, interionic interactions need to be taken into account in the Donnan analysis. Furthermore, the results suggest that the combination of μMRI dGEMRIC experiments and Monte Carlo simulations are useful tools for an improved understanding of these effects. Magn Reson Med 76:500-509, 2016. © 2015 Wiley Periodicals, Inc.
Koerte IK, Willems A, Muehlmann M, Moll K, Cornell S, Pixner S, Steffinger D, Keeser D, Heinen F, Kubicki M, et al. Mathematical abilities in dyslexic children: a diffusion tensor imaging study. Brain Imaging Behav. 2016;10 (3) :781-91.Abstract
Dyslexia is characterized by a deficit in language processing which mainly affects word decoding and spelling skills. In addition, children with dyslexia also show problems in mathematics. However, for the latter, the underlying structural correlates have not been investigated. Sixteen children with dyslexia (mean age 9.8 years [0.39]) and 24 typically developing children (mean age 9.9 years [0.29]) group matched for age, gender, IQ, and handedness underwent 3 T MR diffusion tensor imaging as well as cognitive testing. Tract-Based Spatial Statistics were performed to correlate behavioral data with diffusion data. Children with dyslexia performed worse than controls in standardized verbal number tasks, such as arithmetic efficiency tests (addition, subtraction, multiplication, division). In contrast, the two groups did not differ in the nonverbal number line task. Arithmetic efficiency, representing the total score of the four arithmetic tasks, multiplication, and division, correlated with diffusion measures in widespread areas of the white matter, including bilateral superior and inferior longitudinal fasciculi in children with dyslexia compared to controls. Children with dyslexia demonstrated lower performance in verbal number tasks but performed similarly to controls in a nonverbal number task. Further, an association between verbal arithmetic efficiency and diffusion measures was demonstrated in widespread areas of the white matter suggesting compensatory mechanisms in children with dyslexia compared to controls. Taken together, poor fact retrieval in children with dyslexia is likely a consequence of deficits in the language system, which not only affects literacy skills but also impacts on arithmetic skills.
Koerte IK, Hufschmidt J, Muehlmann M, Tripodis Y, Stamm JM, Pasternak O, Giwerc MY, Coleman MJ, Baugh CM, Fritts NG, et al. Cavum Septi Pellucidi in Symptomatic Former Professional Football Players. J Neurotrauma. 2016;33 (4) :346-53.Abstract
Post-mortem studies reveal a high rate of cavum septi pellucidi (CSP) in chronic traumatic encephalopathy (CTE). It remains, however, to be determined whether or not the presence of CSP may be a potential in vivo imaging marker in populations at high risk to develop CTE. The aim of this study was to evaluate CSP in former professional American football players presenting with cognitive and behavioral symptoms compared with noncontact sports athletes. Seventy-two symptomatic former professional football players (mean age 54.53 years, standard deviation [SD] 7.97) as well as 14 former professional noncontact sports athletes (mean age 57.14 years, SD 7.35) underwent high-resolution structural 3T magnetic resonance imaging. Two raters independently evaluated the CSP, and interrater reliability was calculated. Within National Football League players, an association of CSP measures with cognitive and behavioral functioning was evaluated using a multivariate mixed effects model. The measurements of the two raters were highly correlated (CSP length: rho = 0.98; Intraclass Correlation Coefficient [ICC] 0.99; p < 0.0001; septum length: rho = 0.93; ICC 0.96; p < 0.0001). For presence versus absence of CSP, there was high agreement (Cohen kappa = 0.83, p < 0.0001). A higher rate of CSP, a greater length of CSP, as well as a greater ratio of CSP length to septum length was found in symptomatic former professional football players compared with athlete controls. In addition, a greater length of CSP was associated with decreased performance on a list learning task (Neuropsychological Assessment Battery List A Immediate Recall, p = 0.04) and decreased test scores on a measure of estimate verbal intelligence (Wide Range Achievement Test Fourth Edition Reading Test, p = 0.02). Given the high prevalence of CSP in neuropathologically confirmed CTE in addition to the results of this study, CSP may serve as a potential early in vivo imaging marker to identify those at high risk for CTE. Future research is needed to investigate the pathomechanism underlying the development of CSP after repetitive head impacts, and its potential association with neuropathologically confirmed CTE.
Zhang F, Song Y, Cai W, Liu S, Liu S, Pujol S, Kikinis R, Xia Y, Fulham M, Feng D. Pairwise Latent Semantic Association for Similarity Computation in Medical Imaging. IEEE Trans Biomed Eng. 2016;63 (5) :1058-69.Abstract
Retrieving medical images that present similar diseases is an active research area for diagnostics and therapy. However, it can be problematic given the visual variations between anatomical structures. In this paper, we propose a new feature extraction method for similarity computation in medical imaging. Instead of the low-level visual appearance, we design a CCA-PairLDA feature representation method to capture the similarity between images with high-level semantics. First, we extract the PairLDA topics to represent an image as a mixture of latent semantic topics in an image pair context. Second, we generate a CCA-correlation model to represent the semantic association between an image pair for similarity computation. While PairLDA adjusts the latent topics for all image pairs, CCA-correlation helps to associate an individual image pair. In this way, the semantic descriptions of an image pair are closely correlated, and naturally correspond to similarity computation between images. We evaluated our method on two public medical imaging datasets for image retrieval and showed improved performance.
Avram AV, Sarlls JE, Barnett AS, Özarslan E, Thomas C, Irfanoglu OM, Hutchinson E, Pierpaoli C, Basser PJ. Clinical feasibility of using mean apparent propagator (MAP) MRI to characterize brain tissue microstructure. Neuroimage. 2016;127 :422-34.Abstract
Diffusion tensor imaging (DTI) is the most widely used method for characterizing noninvasively structural and architectural features of brain tissues. However, the assumption of a Gaussian spin displacement distribution intrinsic to DTI weakens its ability to describe intricate tissue microanatomy. Consequently, the biological interpretation of microstructural parameters, such as fractional anisotropy or mean diffusivity, is often equivocal. We evaluate the clinical feasibility of assessing brain tissue microstructure with mean apparent propagator (MAP) MRI, a powerful analytical framework that efficiently measures the probability density function (PDF) of spin displacements and quantifies useful metrics of this PDF indicative of diffusion in complex microstructure (e.g., restrictions, multiple compartments). Rotation invariant and scalar parameters computed from the MAP show consistent variation across neuroanatomical brain regions and increased ability to differentiate tissues with distinct structural and architectural features compared with DTI-derived parameters. The return-to-origin probability (RTOP) appears to reflect cellularity and restrictions better than MD, while the non-Gaussianity (NG) measures diffusion heterogeneity by comprehensively quantifying the deviation between the spin displacement PDF and its Gaussian approximation. Both RTOP and NG can be decomposed in the local anatomical frame for reference determined by the orientation of the diffusion tensor and reveal additional information complementary to DTI. The propagator anisotropy (PA) shows high tissue contrast even in deep brain nuclei and cortical gray matter and is more uniform in white matter than the FA, which drops significantly in regions containing crossing fibers. Orientational profiles of the propagator computed analytically from the MAP MRI series coefficients allow separation of different fiber populations in regions of crossing white matter pathways, which in turn improves our ability to perform whole-brain fiber tractography. Reconstructions from subsampled data sets suggest that MAP MRI parameters can be computed from a relatively small number of DWIs acquired with high b-value and good signal-to-noise ratio in clinically achievable scan durations of less than 10min. The neuroanatomical consistency across healthy subjects and reproducibility in test-retest experiments of MAP MRI microstructural parameters further substantiate the robustness and clinical feasibility of this technique. The MAP MRI metrics could potentially provide more sensitive clinical biomarkers with increased pathophysiological specificity compared to microstructural measures derived using conventional diffusion MRI techniques.
Diaz AA, San José Estépar R, Washko GR. Computed Tomographic Airway Morphology in Chronic Obstructive Pulmonary Disease. Remodeling or Innate Anatomy?. Ann Am Thorac Soc. 2016;13 (1) :4-9.Abstract
Computed tomographic measures of central airway morphology have been used in clinical, epidemiologic, and genetic investigation as an inference of the presence and severity of small-airway disease in smokers. Although several association studies have brought us to believe that these computed tomographic measures reflect airway remodeling, a careful review of such data and more recent evidence may reveal underappreciated complexity to these measures and limitations that prompt us to question that belief. This Perspective offers a review of seminal papers and alternative explanations of their data in the light of more recent evidence. The relationships between airway morphology and lung function are observed in subjects who never smoked, implying that native airway structure indeed contributes to lung function; computed tomographic measures of central airways such as wall area, lumen area, and total bronchial area are smaller in smokers with chronic obstructive pulmonary disease versus those without chronic obstructive pulmonary disease; and the airways are smaller as disease severity increases. The observations suggest that (1) native airway morphology likely contributes to the relationships between computed tomographic measures of airways and lung function; and (2) the presence of smaller airways in those with chronic obstructive pulmonary disease versus those without chronic obstructive pulmonary disease as well as their decrease with disease severity suggests that smokers with chronic obstructive pulmonary disease may simply have smaller airways to begin with, which put them at greater risk for the development of smoking-related disease.
Hardin M, Cho MH, McDonald M-L, Wan E, Lomas DA, Coxson HO, MacNee W, Vestbo J, Yates JC, Agusti A, et al. A genome-wide analysis of the response to inhaled β2-agonists in chronic obstructive pulmonary disease. Pharmacogenomics J. 2016;16 (4) :326-35.Abstract
Short-acting β2-agonist bronchodilators are the most common medications used in treating chronic obstructive pulmonary disease (COPD). Genetic variants determining bronchodilator responsiveness (BDR) in COPD have not been identified. We performed a genome-wide association study (GWAS) of BDR in 5789 current or former smokers with COPD in one African-American and four white populations. BDR was defined as the quantitative spirometric response to inhaled β2-agonists. We combined results in a meta-analysis. In the meta-analysis, single-nucleotide polymorphisms (SNPs) in the genes KCNK1 (P=2.02 × 10(-7)) and KCNJ2 (P=1.79 × 10(-7)) were the top associations with BDR. Among African Americans, SNPs in CDH13 were significantly associated with BDR (P=5.1 × 10(-9)). A nominal association with CDH13 was identified in a gene-based analysis in all subjects. We identified suggestive association with BDR among COPD subjects for variants near two potassium channel genes (KCNK1 and KCNJ2). SNPs in CDH13 were significantly associated with BDR in African Americans.The Pharmacogenomics Journal advance online publication, 27 October 2015; doi:10.1038/tpj.2015.65.
Ning L, Setsompop K, Michailovich O, Makris N, Shenton ME, Westin C-F, Rathi Y. A Joint Compressed-sensing and Super-resolution Approach for Very High-resolution Diffusion Imaging. Neuroimage. 2016;125 :386-400.Abstract
Diffusion MRI (dMRI) can provide invaluable information about the structure of different tissue types in the brain. Standard dMRI acquisitions facilitate a proper analysis (e.g. tracing) of medium-to-large white matter bundles. However, smaller fiber bundles connecting very small cortical or sub-cortical regions cannot be traced accurately in images with large voxel sizes. Yet, the ability to trace such fiber bundles is critical for several applications such as deep brain stimulation and neurosurgery. In this work, we propose a novel acquisition and reconstruction scheme for obtaining high spatial resolution dMRI images using multiple low resolution (LR) images, which is effective in reducing acquisition time while improving the signal-to-noise ratio (SNR). The proposed method called compressed-sensing super resolution reconstruction (CS-SRR), uses multiple overlapping thick-slice dMRI volumes that are under-sampled in q-space to reconstruct diffusion signal with complex orientations. The proposed method combines the twin concepts of compressed sensing and super-resolution to model the diffusion signal (at a given b-value) in a basis of spherical ridgelets with total-variation (TV) regularization to account for signal correlation in neighboring voxels. A computationally efficient algorithm based on the alternating direction method of multipliers (ADMM) is introduced for solving the CS-SRR problem. The performance of the proposed method is quantitatively evaluated on several in-vivo human data sets including a true SRR scenario. Our experimental results demonstrate that the proposed method can be used for reconstructing sub-millimeter super resolution dMRI data with very good data fidelity in clinically feasible acquisition time.
Del Re EC, Gao Y, Eckbo R, Petryshen TL, Blokland GAM, Seidman LJ, Konishi J, Goldstein JM, McCarley RW, Shenton ME, et al. A New MRI Masking Technique Based on Multi-Atlas Brain Segmentation in Controls and Schizophrenia: A Rapid and Viable Alternative to Manual Masking. J Neuroimaging. 2016;26 (1) :28-36.Abstract
UNLABELLED: Brain masking of MRI images separates brain from surrounding tissue and its accuracy is important for further imaging analyses. We implemented a new brain masking technique based on multi-atlas brain segmentation (MABS) and compared MABS to masks generated using FreeSurfer (FS; version 5.3), Brain Extraction Tool (BET), and Brainwash, using manually defined masks (MM) as the gold standard. We further determined the effect of different masking techniques on cortical and subcortical volumes generated by FreeSurfer. METHODS: Images were acquired on a 3-Tesla MR Echospeed system General Electric scanner on five control and five schizophrenia subjects matched on age, sex, and IQ. Automated masks were generated from MABS, FS, BET, and Brainwash, and compared to MM using these metrics: a) volume difference from MM; b) Dice coefficients; and c) intraclass correlation coefficients. RESULTS: Mean volume difference between MM and MABS masks was significantly less than the difference between MM and FS or BET masks. Dice coefficient between MM and MABS was significantly higher than Dice coefficients between MM and FS, BET, or Brainwash. For subcortical and left cortical regions, MABS volumes were closer to MM volumes than were BET or FS volumes. For right cortical regions, MABS volumes were closer to MM volumes than were BET volumes. CONCLUSIONS: Brain masks generated using FreeSurfer, BET, and Brainwash are rapidly obtained, but are less accurate than manually defined masks. Masks generated using MABS, in contrast, resemble more closely the gold standard of manual masking, thereby offering a rapid and viable alternative.
Savadjiev P, Seidman LJ, Thermenos H, Keshavan M, Whitfield-Gabrieli S, Crow TJ, Kubicki M. Sexual dimorphic abnormalities in white matter geometry common to schizophrenia and non-psychotic high-risk subjects: Evidence for a neurodevelopmental risk marker?. Hum Brain Mapp. 2016;37 (1) :254-61.Abstract
The characterization of neurodevelopmental aspects of brain alterations require neuroimaging methods that reflect correlates of neurodevelopment, while being robust to other progressive pathological processes. Newly developed neuroimaging methods for measuring geometrical features of the white matter fall exactly into this category. Our recent work shows that such features, measured in the anterior corpus callosum in diffusion MRI data, correlate with psychosis symptoms in patients with adolescent onset schizophrenia and subside a reversal of normal sexual dimorphism. Here, we test the hypothesis that similar developmental deviations will also be present in nonpsychotic subjects at familial high risk (FHR) for schizophrenia, due to genetic predispositions. Demonstrating such changes would provide a strong indication of neurodevelopmental deviation extant before, and independent of pathological changes occurring after disease onset. We examined the macrostructural geometry of corpus callosum white matter in diffusion MRI data of 35 non-psychotic subjects with genetic (familial) risk for schizophrenia, and 26 control subjects, both male and female. We report a reversal of normal sexual dimorphism in callosal white matter geometry consistent with recent results in adolescent onset schizophrenia. This pattern may be indicative of an error in neurogenesis and a possible trait marker of schizophrenia.
Makris N, Rathi Y, Mouradian P, Bonmassar G, Papadimitriou G, Ing WI, Yeterian EH, Kubicki M, Eskandar EN, Wald LL, et al. Variability and anatomical specificity of the orbitofrontothalamic fibers of passage in the ventral capsule/ventral striatum (VC/VS): precision care for patient-specific tractography-guided targeting of deep brain stimulation (DBS) in obsessive compulsive. Brain Imaging Behav. 2016;10 (4) :1054-1067.Abstract
Deep Brain Stimulation (DBS) is a neurosurgical procedure that can reduce symptoms in medically intractable obsessive-compulsive disorder (OCD). Conceptually, DBS of the ventral capsule/ventral striatum (VC/VS) region targets reciprocal excitatory connections between the orbitofrontal cortex (OFC) and thalamus, decreasing abnormal reverberant activity within the OFC-caudate-pallidal-thalamic circuit. In this study, we investigated these connections using diffusion magnetic resonance imaging (dMRI) on human connectome datasets of twenty-nine healthy young-adult volunteers with two-tensor unscented Kalman filter based tractography. We studied the morphology of the lateral and medial orbitofrontothalamic connections and estimated their topographic variability within the VC/VS region. Our results showed that the morphology of the individual orbitofrontothalamic fibers of passage in the VC/VS region is complex and inter-individual variability in their topography is high. We applied this method to an example OCD patient case who underwent DBS surgery, formulating an initial proof of concept for a tractography-guided patient-specific approach in DBS for medically intractable OCD. This may improve on current surgical practice, which involves implanting all patients at identical stereotactic coordinates within the VC/VS region.
Cho KIK, Shenton ME, Kubicki M, Jung WH, Lee TY, Yun J-Y, Kim SN, Kwon JS. Altered Thalamo-Cortical White Matter Connectivity: Probabilistic Tractography Study in Clinical-High Risk for Psychosis and First-Episode Psychosis. Schizophr Bull. 2016;42 (3) :723-31.Abstract
Disrupted thalamo-cortical connectivity is regarded as a core psychopathology in patients diagnosed with schizophrenia. However, whether the thalamo-cortical white matter connectivity is disrupted before the onset of psychosis is still unknown. To determine this gap in knowledge, the strength of thalamo-cortical white matter anatomical connectivity in subjects at clinical-high risk for psychosis (CHR) was compared to that of first-episode psychosis (FEP) and healthy controls. A total of 37 CHR, 21 FEP, and 37 matched healthy controls underwent diffusion-weighted magnetic resonance imaging to examine the number of probabilistic tractography "counts" representing thalamo-cortical white matter connectivity. We also investigated the relationship with psychopathology. For FEP, the connectivity between the thalamus and parietal cortex was significantly increased (F= 5.65,P< .05) compared to that of healthy controls. However, the connectivity between thalamus and orbitofrontal cortex was significantly reduced compared to both healthy controls (F= 11.86,P< .005) and CHR (F= 6.63,P< .05). Interestingly, CHR exhibited a similar pattern as FEP, albeit with slightly reduced magnitude. Compared to healthy controls, there was a significant decrease (F= 4.16,P< .05) in CHR thalamo-orbitofrontal connectivity. Also, the strength of the thalamo-orbitofrontal connectivity was correlated with the Global Assessment of Functioning score in CHR (r= .35,P< .05). This observed pattern of white matter connectivity disruptions in FEP and in CHR suggests that this pattern of disconnectivity not only highlights the involvement of thalamus but also might be useful as an early biomarker for psychosis.
Jimenez-Carretero D, Estepar RSJ, Diaz Cacio M, Ledesma-Carbayo MJ. Automatic Synthesis of Anthropomorphic Pulmonary CT Phantoms. PLoS One. 2016;11 (1) :e0146060.Abstract
The great density and structural complexity of pulmonary vessels and airways impose limitations on the generation of accurate reference standards, which are critical in training and in the validation of image processing methods for features such as pulmonary vessel segmentation or artery-vein (AV) separations. The design of synthetic computed tomography (CT) images of the lung could overcome these difficulties by providing a database of pseudorealistic cases in a constrained and controlled scenario where each part of the image is differentiated unequivocally. This work demonstrates a complete framework to generate computational anthropomorphic CT phantoms of the human lung automatically. Starting from biological and image-based knowledge about the topology and relationships between structures, the system is able to generate synthetic pulmonary arteries, veins, and airways using iterative growth methods that can be merged into a final simulated lung with realistic features. A dataset of 24 labeled anthropomorphic pulmonary CT phantoms were synthesized with the proposed system. Visual examination and quantitative measurements of intensity distributions, dispersion of structures and relationships between pulmonary air and blood flow systems show good correspondence between real and synthetic lungs (p > 0.05 with low Cohen's d effect size and AUC values), supporting the potentiality of the tool and the usefulness of the generated phantoms in the biomedical image processing field.
Cros O, Knutsson H, Andersson M, Pawels E, Borga M, Gaihede M. Determination of the mastoid surface area and volume based on micro-CT scanning of human temporal bones. Geometrical parameters depend on scanning resolutions. Hear Res. 2016;340 :127-134.Abstract
The mastoid air cell system (MACS) with its large complex of interconnected air cells reflects an enhanced surface area (SA) relative to its volume (V), which may indicate that the MACS is adapted to gas exchange and has a potential role in middle ear pressure regulation. These geometric parameters of the MACS have been studied by high resolution clinical CT scanning. However, the resolution of these scans is limited to a voxel size of around 0.6 mm in all dimensions, and so, the geometrical parameters are also limited. Small air cells may appear below the resolution and cannot be detected. Such air cells may contribute to a much higher SA, and thus, also the SA/V ratio. More accurate parameters are important for analysis of the function of the MACS including physiological modeling. Our aim was to determine the SA, V, and SA/V ratio in the MACS in human temporal bones at highest resolution by using micro-CT-scanning. Further, the influence of the resolution on these parameters was investigated by downsampling the data. Eight normally aerated temporal bones were scanned at the highest possible resolution (30-60 μm). The SA was determined using a triangular mesh fitted onto the segmented MACS. The V was determined by summing all the voxels containing air. Downsampling of the original data was applied four times by a factor of 2. The mean SA was 194 cm(2), the mean V was 9 cm(3), and the mean SA/V amounted to 22 cm(-1) (22 cm(2)/cm(3)). Decreasing the resolution resulted in a non-linear decrement of SA and SA/V, whereas V was mainly independent of the resolution. The current study found significantly higher SA and SA/V compared with previous studies using clinical CT scanning at lower resolutions. These findings indicate a role of the MACS different from that of the tympanum, though they are limited to only a smaller sample of temporal bones without knowledge about the disease history of the subjects. The current data on mastoid geometry seems important for a more accurate modeling of the middle ear physiology and future studies may include morphological investigations of the air cells with possible implications for their postnatal development.
Del Re EC, Konishi J, Bouix S, Blokland GAM, Mesholam-Gately RI, Goldstein J, Kubicki M, Wojcik J, Pasternak O, Seidman LJ, et al. Enlarged lateral ventricles inversely correlate with reduced corpus callosum central volume in first episode schizophrenia: association with functional measures. Brain Imaging Behav. 2016;10 (4) :1264-1273.Abstract
The lateral and third ventricles, as well as the corpus callosum (CC), are known to be affected in schizophrenia. Here we investigate whether abnormalities in the lateral ventricles (LVs), third ventricle, and corpus callosum are related to one another in first episode schizophrenia (FESZ), and whether such abnormalities show progression over time. Nineteen FESZ and 19 age- and handedness-matched controls were included in the study. MR images were acquired on a 3-Tesla MRI at baseline and ~1.2 years later. FreeSurfer v.5.3 was employed for segmentation. Two-way or univariate ANCOVAs were used for statistical analysis, where the covariate was intracranial volume. Group and gender were included as between-subjects factors. Percent volume changes between baseline and follow-up were used to determine volume changes at follow-up. Bilateral LV and third ventricle volumes were significantly increased, while central CC volume was significantly decreased in patients compared to controls at baseline and at follow-up. In FESZ, the bilateral LV volume was also inversely correlated with volume of the central CC. This inverse correlation was not present in controls. In FESZ, an inverse correlation was found between percent volume increase from baseline to follow-up for bilateral LVs and lesser improvement in the Global Assessment of Functioning score. Significant correlations were observed for abnormalities of central CC, LVs and third ventricle volumes in FESZ, suggesting a common neurodevelopmental origin in schizophrenia. Enlargement of ventricles was associated with less improvement in global functioning over time.
Planetta PJ, Ofori E, Pasternak O, Burciu RG, Shukla P, DeSimone JC, Okun MS, McFarland NR, Vaillancourt DE. Free-water imaging in Parkinson's disease and atypical parkinsonism. Brain. 2016;139 (Pt 2) :495-508.Abstract
Conventional single tensor diffusion analysis models have provided mixed findings in the substantia nigra of Parkinson's disease, but recent work using a bi-tensor analysis model has shown more promising results. Using a bi-tensor model, free-water values were found to be increased in the posterior substantia nigra of Parkinson's disease compared with controls at a single site and in a multi-site cohort. Further, free-water increased longitudinally over 1 year in the posterior substantia nigra of Parkinson's disease. Here, we test the hypothesis that other parkinsonian disorders such as multiple system atrophy and progressive supranuclear palsy have elevated free-water in the substantia nigra. Equally important, however, is whether the bi-tensor diffusion model is able to detect alterations in other brain regions beyond the substantia nigra in Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy and to accurately distinguish between these diseases. Free-water and free-water-corrected fractional anisotropy maps were compared across 72 individuals in the basal ganglia, midbrain, thalamus, dentate nucleus, cerebellar peduncles, cerebellar vermis and lobules V and VI, and corpus callosum. Compared with controls, free-water was increased in the anterior and posterior substantia nigra of Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy. Despite no other changes in Parkinson's disease, we observed elevated free-water in all regions except the dentate nucleus, subthalamic nucleus, and corpus callosum of multiple system atrophy, and in all regions examined for progressive supranuclear palsy. Compared with controls, free-water-corrected fractional anisotropy values were increased for multiple system atrophy in the putamen and caudate, and increased for progressive supranuclear palsy in the putamen, caudate, thalamus, and vermis, and decreased in the superior cerebellar peduncle and corpus callosum. For all disease group comparisons, the support vector machine 10-fold cross-validation area under the curve was between 0.93-1.00 and there was high sensitivity and specificity. The regions and diffusion measures selected by the model varied across comparisons and are consistent with pathological studies. In conclusion, the current study used a novel bi-tensor diffusion analysis model to indicate that all forms of parkinsonism had elevated free-water in the substantia nigra. Beyond the substantia nigra, both multiple system atrophy and progressive supranuclear palsy, but not Parkinson's disease, showed a broad network of elevated free-water and altered free-water corrected fractional anisotropy that included the basal ganglia, thalamus, and cerebellum. These findings may be helpful in the differential diagnosis of parkinsonian disorders, and thereby facilitate the development and assessment of targeted therapies.
Li Z, Liu M, Lan L, Zeng F, Makris N, Liang Y, Guo T, Wu F, Gao Y, Dong M, et al. Altered periaqueductal gray resting state functional connectivity in migraine and the modulation effect of treatment. Sci Rep. 2016;6 :20298.Abstract
The aims of this study were to 1) compare resting state functional connectivity (rs-fc) of the periaqueductal gray (PAG), a key region in the descending pain modulatory system (DPMS) between migraine without aura (MwoA) patients and healthy controls (HC), and 2) investigate how an effective treatment can influence the PAG rs-fc in MwoA patients. One hundred MwoA patients and forty-six matched HC were recruited. Patients were randomized to verum acupuncture, sham acupuncture, and waiting list groups. Resting state fMRI data were collected and seed based functional connectivity analysis was applied. Compared with HC, MwoA patients showed reduced rs-fc between the PAG and rostral anterior cingulate cortex/medial prefrontal cortex (rACC/mPFC), key regions in the DPMS and other pain related brain regions. The reduced rs-fc between the PAG and rACC/mPFC was associated with increased migraine headache intensity at the baseline. After treatments, rs-fc between the PAG and the rACC in MwoA patients significantly increased. The changes of rs-fc among the PAG, rACC and ventral striatum were significantly associated with headache intensity improvement. Impairment of the DPMS is involved in the neural pathophysiology of migraines. Impaired DPMS in migraine patients can be normalized after effective treatment.

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