Commissioning and validation of commercial deformable image registration software for adaptive contouring

PurposeTo report the commissioning and validation of deformable image registration(DIR) software for adaptive contouring.MethodsDIR (SmartAdapt®v13.6) was validated using two methods namely contour propagation accuracy and landmark tracking, using physical phantoms and clinical images of various disease sites. Five in-house made phantoms with various known deformations and a set of 10 virtual phantoms were used. Displacement in lateral, anterio-posterior (AP) and superior-inferior (SI) direction were evaluated for various organs and compared with the ground truth. Four clinical sites namely, brain (n = 5), HN (n = 9), cervix (n = 18) and prostate (n = 23) were used. Organs were manually delineated by a radiation oncologist, compared with the deformable image registration (DIR) generated contours. 3D slicer v4.5.0.1 was used to analyze Dice Similarity Co-efficient (DSC), shift in centre of mass (COM) and Hausdorff distances Hf_95%/avg.ResultsMean (SD) DSC, Hf_95% (mm), Hf_avg (mm) and COM of all the phantoms 1–5 were 0.84 (0.2) mm, 5.1 (7.4) mm, 1.6 (2.2) mm, and 1.6 (0.2) mm respectively. Phantom-5 had the largest deformation as compared to phantoms 1–4, and hence had suboptimal indices. The virtual phantom resulted in consistent results for all the ROIs investigated. Contours propagated for brain patients were better with a high DSC score (0.91 (0.04)) as compared to other sites (HN: 0.84, prostate: 0.81 and cervix 0.77). A similar trend was seen in other indices too. The accuracy of propagated contours is limited for complex deformations that include large volume and shape change of bladder and rectum respectively. Visual validation of the propagated contours is recommended for clinical implementation.ConclusionThe DIR algorithm was commissioned and validated for adaptive contouring.     

A quantitative evaluation of deformable image registration based on MV cone beam CT images: Impact of deformation magnitudes and image modalities

Background and purposeTo evaluate the impact of deformation magnitude and image modality on deformable-image-registration (DIR) accuracy using Halcyon megavoltage cone beam CT images (MVCBCT).Materials and methodsPlanning CT images of an anthropomorphic Head phantom were aligned rigidly with MVCBCT and re-sampled to achieve the same resolution, denoted as pCT. MVCBCT was warped with twenty simulated pre-known virtual deformation fields (T_i, i = 1–20) with increasing deformation magnitudes, yielding warped CBCT (wCBCT). The pCT and MVCBCT were registered to wCBCT respectively (Multi-modality and Uni-modality DIR), generating deformation vector fields V_i and V_i′ (i = 1–20). V_i and V_i′ were compared with T_i respectively to assess the DIR accuracy geometrically. In addition, V_i, T_i, and V_i′ were applied to pCT, generating deformed CT (dCT_i), ground-truth CT (G_i) and deformed CT′ (dCT_i′) respectively. The Hounsfield Unit (HU) on these virtual CT images were also compared.ResultsThe mean errors of vector displacement increased with the deformation magnitude. For deformation magnitudes between 2.82 mm and 7.71 mm, the errors of uni-modality DIR were 1.16 mm ~ 1.73 mm smaller than that of multi-modality (p = 0.0001, Wilcoxon signed rank test). DIR could reduce the maximum signed and absolute HU deviations from 70.8 HU to 11.4 HU and 208 HU to 46.2 HU respectively.ConclusionsAs deformation magnitude increases, DIR accuracy continues to deteriorate and uni-modality DIR consistently outperformed multi-modality DIR. DIR-based adaptive radiotherapy utilizing the noisy MVCBCT images is only conditionally applicable with caution.     

Development of a dynamic deformable thorax phantom for the quality management of deformable image registration

The purpose of this study was to develop a novel dynamic deformable thorax phantom for deformable image registration (DIR) quality assurance (QA) and to verify as a tool for commissioning and DIR QA.The phantom consists of a base phantom, an inner phantom, and a motor-derived piston. The base phantom is an acrylic cylinder phantom with a diameter of 180 mm. The inner phantom consists of deformable, 20 mm thick disk-shaped sponges. To evaluate the physical characteristics of the phantom, we evaluated its image quality and deformation. DIR accuracies were evaluated using the three types of commercially DIR software (MIM, RayStation, and Velocity AI) to test the feasibility of this phantom. We used different DIR parameters to test the impact of parameters on DIR accuracy in various phantom settings. To evaluate DIR accuracy, a target registration error (TRE) was calculated using the anatomical landmark points.The three locations (i.e., distal, middle, and proximal positions) had different displacement amounts. This result indicated that the inner phantom was not moved but deformed. In cases with different phantom settings and marker settings, the ranges of the average TRE were 0.63–15.60 mm (MIM). In cases with different DIR parameters settings, the ranges of the average TRE were as follows: 0.73–7.10 mm (MIM), 8.25–8.66 mm (RayStation), and 8.26–8.43 mm (Velocity). These results suggest that our phantom could evaluate the detailed DIR behaviors with TRE. Therefore, this is indicative of the potential usefulness of our phantom in DIR commissioning and QA.     

A validation framework to assess performance of commercial deformable image registration in lung radiotherapy

IntroductionDeformable image registration (DIR) can play an important role in the context of adaptive radiotherapy. The AAPM Task Group 132 (TG-132) has described several quantitative measures for DIR error assessment but they can only be accurately defined when there is a ground-truth present in high-contrast regions. This work aims to set out a framework to obtain optimal results for CT-CT lung DIR in clinical setting for a commercially available system by quantifying the DIR performance in both low- and high-contrast regions.MethodsFive publicly available thorax datasets were used to assess the DIR quality. A “Ghost fiducial” method was implemented by windowing the contrast in a new feature provided by Varian Velocity v4.1. Target registration error (TRE) of the landmarks and Dice-similarity coefficient of the tumour were calculated at three different contrast settings to assess the algorithm in high- and low-contrast scenarios.ResultsFor the original unedited dataset, higher resolution DIR methods showed best performance acceptable within the recommended limit according to TG-132, when actual displacements were less than 10 mm. The relation of the actual displacement of the landmarks and TRE shows the limited capacity of the algorithm to deal with movements larger than 10 mm.ConclusionThis work found the performance of DIR methods and settings available in Varian Velocity v4.1 to be a function of contrast level as well as extent of motion. This highlights the need for multiple metrics to assess different aspects of DIR performance for various applications related to low-contrast and/or high-contrast regions.     

Effect of image registration on 3D absorbed dose calculations in 177Lu-DOTATOC peptide receptor radionuclide therapy

Peptide receptor radionuclide therapy (PRRT) is an effective MRT (molecular radiotherapy) treatment, which consists of multiple administrations of a radiopharmaceutical labelled with ¹⁷⁷Lu or ⁹⁰Y. Through sequential functional imaging a patient specific 3D dosimetry can be derived. Multiple scans should be previously co-registered to allow accurate absorbed dose calculations. The purpose of this study is to evaluate the impact of image registration algorithms on 3D absorbed dose calculation.A cohort of patients was extracted from the database of a clinical trial in PRRT. They were administered with a single administration of ¹⁷⁷Lu-DOTATOC. All patients underwent 5 SPECT/CT sequential scans at 1 h, 4 h, 24 h, 40 h, 70 h post-injection that were subsequently registered using rigid and deformable algorithms. A similarity index was calculated to compare rigid and deformable registration algorithms. 3D absorbed dose calculation was carried out with the Raydose Monte Carlo code.The similarity analysis demonstrated the superiority of the deformable registrations (p < .001).Average absorbed dose to the kidneys calculated using rigid image registration was consistently lower than the average absorbed dose calculated using the deformable algorithm (90% of cases), with percentage differences in the range [−19; +4]%. Absorbed dose to lesions were also consistently lower (90% of cases) when calculated with rigid image registration with absorbed dose differences in the range [−67.2; 100.7]%. Deformable image registration had a significant role in calculating 3D absorbed dose to organs or lesions with volumes smaller than 100 mL.Image based 3D dosimetry for ¹⁷⁷Lu-DOTATOC PRRT is significantly affected by the type of algorithm used to register sequential SPECT/CT scans.     

Validation of a deformable image registration produced by a commercial treatment planning system in head and neck

In recent years one of the areas of interest in radiotherapy has been adaptive radiation therapy (ART), with the most efficient way of performing ART being the use of deformable image registration (DIR). In this paper we use the distances between points of interest (POIs) in the computed tomography (CT) and the cone beam computed tomography (CBCT) acquisition images and the inverse consistence (IC) property to validate the RayStation treatment planning system (TPS) DIR algorithm. This study was divided into two parts: Firstly the distance-accuracy of the TPS DIR algorithm was ascertained by placing POIs on anatomical features in the CT and CBCT images from five head and neck cancer patients. Secondly, a method was developed for studying the implication of these distances on the dose by using the IC. This method compared the dose received by the structures in the CT, and the structures that were quadruply-deformed. The accuracy of the TPS was 1.7 ± 0.8 mm, and the distance obtained with the quadruply-deformed IC method was 1.7 ± 0.9 mm, i.e. the difference between the IC method multiplied by two, and that of the TPS validation method, was negligible. Moreover, the IC method shows very little variation in the dose-volume histograms when comparing the original and quadruply-deformed structures. This indicates that this algorithm is useful for planning adaptive radiation treatments using CBCT in head and neck cancer patients, although these variations must be taken into account when making a clinical decision to adapt a treatment plan.     

Influence of different urinary bladder filling levels and controlling regions of interest selection on deformable image registration algorithms

PurposeEvaluation of Raystation ANAtomically CONstrained Deformation Algorithm (ANACONDA) performance to different urinary bladder filling levels in male pelvis anatomic site varying the controlling Regions Of Interest (ROIs).MethodsDifferent image datasets were obtained with ImSimQA (Oncology System Limited, Shrewsbury, UK) to evaluate ANACONDA performances (RaySearch Laboratories, Stockholm, Sweden). Deformation vector fields were applied to a synthetic man pelvis and a real patient computed tomography (CT) dataset (reference CTs) resulting in deformed CTs (target CTs) with various bladder filling levels. Different deformable image registrations (DIRs) were generated between each target CTs and reference CTs varying the controlling ROIs subset. Deformed ROIs were mapped from target CT to reference CT and then compared to reference ROIs. Evaluation was performed by Dice Similarity Coefficient (DSC), Correlation Coefficient (CC), Mean Distance to Agreement (MDA), maximum Distance to Agreement (maxDA) and with the introduction of global DSC (global_DSC) and global CC (global_CC) parameters.ResultsIn both synthetic and real patient CT cases, DSC scored less than 0.75 and MDA greater than 3 mm when no ROIs or only bladder were exploited as controlling ROI. DSC and CC increased by increasing the number of controlling ROIs selected whereas, an opposite behavior was observed for MDA and maxDA.ConclusionsANACONDA performances can be influenced by bladder filling fluctuation if no controlling ROIs are selected. Global_DSC and global_CC are useful parameters to quantitatively compare DIR algorithms. DIR performances improve by increasing the number of controlling ROIs selected, reaching a saturation level after a defined ROIs subset selection.     

Accuracy of target delineation by positron emission tomography-based auto-segmentation methods after deformable image registration: A phantom study

PurposeDiagnostic positron emission tomography and computed tomography (PET/CT) images can be fused to the planning CT images by a deformable image registration (DIR). The aim of this study was to evaluate the standardized uptake value (SUV) and target delineation on deformed PET images.MethodsWe used a cylindrical phantom and removable inserts of four spheres (16–38 mm in diameter) and three ellipsoids with a volume equal to the 38-mm-diameter sphere (S38) in each. S38 was filled with 18F-fluorodeoxyglucose activity, and then PET/CT images were acquired. The contours of S38 were generated using original PET images by PET auto-segmentation (PET-AS) methods of (1) SUV2.5, (2) 40% of maximum SUV (SUV40%max), and (3) gradient-based (GB), and were deformed to the other inserts by DIR. We compared the volumes and the SUV_max with the generated contours using the deformed PET images.ResultsThe SUV_max was slightly decreased by DIR; the mean absolute difference was −0.10 ± 0.04. For SUV2.5 and SUV40%max, the differences in S38 volumes between the original and deformed PET images were less than 5%, regardless of deformation type. For the GB, the contoured volumes obtained from deformed PET images were larger than those of the original PET images for the deformation type of ellipsoids. When the S38 was deformed to the 16-mm-diameter sphere, the maximum volume difference was −22.8%.ConclusionsAlthough SUV fluctuations by DIR were negligible, the target delineation on deformed PET images by the GB should be carefully considered owing to the distortion of intensity profiles.     

The utility of deformable image registration for small artery visualisation in contrast-enhanced whole body MR angiography

PurposeAn investigation was carried out into the effect of three image registration techniques on the diagnostic image quality of contrast-enhanced magnetic resonance angiography (CE-MRA) images.MethodsWhole-body CE-MRA data from the lower legs of 27 patients recruited onto a study of asymptomatic atherosclerosis were processed using three deformable image registration algorithms. The resultant diagnostic image quality was evaluated qualitatively in a clinical evaluation by four expert observers, and quantitatively by measuring contrast-to-noise ratios and volumes of blood vessels, and assessing the techniques' ability to correct for varying degrees of motion.ResultsThe first registration algorithm (‘AIR’) introduced significant stenosis-mimicking artefacts into the blood vessels' appearance, observed both qualitatively (clinical evaluation) and quantitatively (vessel volume measurements). The two other algorithms (‘Slicer’ and ‘SEMI’), based on the normalised mutual information (NMI) concept and designed specifically to deal with variations in signal intensity as found in contrast-enhanced image data, did not suffer from this serious issue but were rather found to significantly improve the diagnostic image quality both qualitatively and quantitatively, and demonstrated a significantly improved ability to deal with the common problem of patient motion.ConclusionsThis work highlights both the significant benefits to be gained through the use of suitable registration algorithms and the deleterious effects of an inappropriate choice of algorithm for contrast-enhanced MRI data. The maximum benefit was found in the lower legs, where the small arterial vessel diameters and propensity for leg movement during image acquisitions posed considerable problems in making accurate diagnoses from the un-registered images.     

MR image analysis of ex-vivo mouse model of heart ischemia

IntroductionMyocardial infarction is one of the major causes of death and disability. Various diagnostic modalities used to investigate cardiac ischaemia. Advances in Magnetic Resonance Imaging technology has opened up new horizons for investigating the cardiac function and quantifying any pathology that may be present.AimsThe present study was designed to quantify the cardiac area at risk and infarction reperfusion areas using the mismatch of iron oxide contrast and gadolinium (Gd) contrast imaging (MRIs) and to test if a combination of T1, T2, and iron oxide T2* contrasts will distinguish the infarction and AAR zones.MethodsA well-established mouse model was used to induced cardiac ischaemia and reperfusion. Six mice models’ hearts were harvested and processed according to various protocols. MI was induced through ligation technique for five mice, and one was kept as normal control. MR imaging and Reperfusion were performed using a Three-dimensional gradient-echo fast low angle shot (3DFLASH) and three-dimensional multi-slice multi-echo sequence (3DMSME). Generation of T1 and T2 maps, image post-processing including segmentation and mismatch measurement and drawing of the area of interest.ResultsThe edematous myocardium had significant high signal intensity in 3DMSME with variable echo time (14, 28, 42 ms). The combination of 3DFLASH and 3DMSME at an echo time of 42 ms was statistically significant, detecting the AAR more accurately. Both T1 and T2 sequences had the potential to determine the AAR zone. The infarct area has significantly high signal intensity compared to normal areas (p = 0.04 for the T1 map and p = 0.01 for the T2 map).ConclusionsThe study demonstrated that Cardiac MRI was a valuable technology to investigate infarct areas and zones that are at risk.     

核磁共振检测大鼠早期癫痫源性脑损伤的动态发展特征

为探讨癫痫源性脑损伤形成早期不同脑区病理改变和行为发作的动态发展特征 ,本研究对大鼠右背侧海马 (hippocampus,HPC)施加慢性强直电刺激 (6 0Hz,2s,0 .4～ 0 .6mA)诱发癫痫发作 ,1次 /d。每天记录大鼠原发性湿狗样抖动 (wetdogshakes,WEDS)频率 ,分别对大鼠施加电刺激 2、4、6、8和 10d后进行核磁共振成像 (T2 weightedmagneticresonanceimage ,T2 WI)检测 ,并对鼠脑进行了组织学切片鉴定。结果表明 :与空白对照组相比较 ,(1)施加 2d强直电刺激时 ,大鼠双侧背部侧脑室 (lateralventricle,LV)区域呈现对称性T2 WI信号绝对值增加 (n =4,左侧P =0 .0 0 18;右侧P =0 .0 0 10 ) ;施加 6d强直电刺激时 ,大鼠呈现植入电极对侧中、腹部LV区域T2 WI信号值增加 (n =5 ,P =0 .0 0 73;P =0 .0 2 49) ;施加 8d强直电刺激后 ,大鼠仅出现植入电极对侧腹部LV区域T2 WI信号值增加 (n =3,P =0 .0 34 0 ) ;施加 10d强直电刺激后 ,大鼠植入电极同侧腹部LV区域T2 WI信号值增加 (n =4,P =0 .0 10 7) ;(2 )随着强直电刺激天数增加 ,大鼠原发性WEDS频率高峰期出现在第 4个刺激日 ,然后WEDS频率下降 ,与T2 WI信号强度增加之间呈高度负相关关系 (相关系数r =- 0 .987,P <0 .0 2 ) ;(3)组织学切片鉴定 :T2 WI检测LV信号异     

Deep learning image analysis models pretrained on daily objects are useful for the preliminary characterization of particulate pharmaceutical samples

Visible and subvisible particles are a quality attribute in sterile pharmaceutical samples. A common method for characterizing and quantifying pharmaceutical samples containing particulates is imaging many individual particles using high-throughput instrumentation and analyzing the populations data. The analysis includes conventional metrics such as the particle size distribution but can be more sophisticated by interpreting other visual/morphological features. To avoid the hurdles of building new image analysis models capable of extracting such relevant features from scratch, we propose using well-established pretrained deep learning image analysis models such as EfficientNet. We demonstrate that such models are useful as a prescreening tool for high-level characterization of biopharmaceutical particle image data. We show that although these models are originally trained for completely different tasks (such as the classification of daily objects in the ImageNet database), the visual feature vectors extracted by such models can be useful for studying different types of subvisible particles. This applicability is illustrated through multiple case studies: (i) particle risk assessment in prefilled syringe formulations containing different particle types such as silicone oil, (ii) method comparability with the example of accelerated forced degradation, and (iii) excipient influence on particle morphology with the example of Polysorbate 80 (PS80). As examples of agnostic applicability of pretrained models, we also elucidate the application to two high-throughput microscopy methods: microflow and background membrane imaging. We show that different particle populations with different morphological and visual features can be identified in different samples by leveraging out-of-the-box pretrained models to analyze images from each sample.     

Sensitivity of MRI signal distribution within the intervertebral disc to image segmentation and data normalisation

There is a lack of early biomarkers of intervertebral disc (IVD) degeneration. Thus, the authors developed the analysis of magnetic resonance signal intensity distribution (AMRSID) method to analyse the 3D distribution of the T2-weighted MR signal intensity within the IVD using normalised histograms, weighted centres and volume ratios. The objective was to assess the sensitivity of the AMRSID method to the segmentation process and data normalisation. Repetition of the semi-automatic segmentation by the same operator did not influence the quality of the contour or our new MR distribution parameters whereas the skills of the operator influenced only the MR distribution parameters, and the instructions given prior to the segmentation influenced both the quality of the contour and the MR distribution parameters. Bone normalisation produces an index that jointly highlights IVD and bone health, whereas cerebrospinal fluid normalisation only suppresses the effect of the acquisition gain. This robust AMRSID method has the potential to improve the diagnostic with earlier biomarkers and the prognosis of evolution.     

组织学与核磁共振检测大鼠癫痫源性早期脑损伤的跨半球扩布特征

侵性强直电刺激(60Hz,2s)大鼠右侧背海马(hippocampus,DHPC)CAl基树突区,1次/d,连续刺激10d。分别在施加强直电刺激的第2、4、6、8或10d时进行核磁共振成像检测(T2 weighted magnetic resonamce image T2-WI),并对鼠脑进行组织学切片鉴定。结果表明,早期慢性癫痫源性脑损伤的病理性形态特征主要包括：(1)T2-WI检测侧脑室(lateral ventricle,LV)区域信号增强、组织学检测LV扩大和双侧对称性脉络膜丛病理性增生,后两者并非完全平行呈现。(2)组织学切片显示双侧LV扩大面积与T2-WI信号增强区域面积的脑区分布近似。与空白对照组大鼠相比,电刺激2、4、6、8和10d后,T2-WI信号增强区域面积显著增大(P=0．0259;P＝0．0184;P=0．0184;P＝0．0404;P＝0．0259)以及组织学鉴定LV面积增大(P＝0．0210;P＝0．01;P＝0．0100;P=0．0152).(3)定侧分析显示,T2-WI信号增强以及T2-WI信号增强区域面积和组织学鉴定LV面积扩大,在慢性刺激6d时均以植入电极的对侧为主;第10d时均以同侧为主。三项观察结果的一致性证实了癫痫源性早期脑损伤的跨半球动态扩布特征。     

Application of a semi-automatic cartilage segmentation method for biomechanical modeling of the knee joint

Manual segmentation of articular cartilage from knee joint 3D magnetic resonance images (MRI) is a time consuming and laborious task. Thus, automatic methods are needed for faster and reproducible segmentations. In the present study, we developed a semi-automatic segmentation method based on radial intensity profiles to generate 3D geometries of knee joint cartilage which were then used in computational biomechanical models of the knee joint. Six healthy volunteers were imaged with a 3T MRI device and their knee cartilages were segmented both manually and semi-automatically. The values of cartilage thicknesses and volumes produced by these two methods were compared. Furthermore, the influences of possible geometrical differences on cartilage stresses and strains in the knee were evaluated with finite element modeling. The semi-automatic segmentation and 3D geometry construction of one knee joint (menisci, femoral and tibial cartilages) was approximately two times faster than with manual segmentation. Differences in cartilage thicknesses, volumes, contact pressures, stresses, and strains between segmentation methods in femoral and tibial cartilage were mostly insignificant (p > 0.05) and random, i.e. there were no systematic differences between the methods. In conclusion, the devised semi-automatic segmentation method is a quick and accurate way to determine cartilage geometries; it may become a valuable tool for biomechanical modeling applications with large patient groups.     

MRI metrics at the epicenter of spinal cord injury are correlated with the stepping process in rhesus monkeys

Clinical evaluations of long-term outcomes in the early-stage spinal cord injury (SCI) focus on macroscopic motor performance and are limited in their prognostic precision. This study was designed to investigate the sensitivity of the magnetic resonance imaging (MRI) indexes to the data-driven gait process after SCI. Ten adult female rhesus monkeys were subjected to thoracic SCI. Kinematics-based gait examinations were performed at 1 (early stage) and 12 (chronic stage) months post-SCI. The proportion of stepping (PS) and gait stability (GS) were calculated as the outcome measures. MRI metrics, which were derived from structural imaging (spinal cord cross-sectional area, SCA) and diffusion tensor imaging (fractional anisotropy, FA; axial diffusivity, λ_//), were acquired in the early stage and compared with functional outcomes by using correlation analysis and stepwise multivariable linear regression. Residual tissue SCA at the injury epicenter and residual tissue FA/remote normal-like tissue FA were correlated with the early-stage PS and GS. The extent of lesion site λ_///residual tissue λ_// in the early stage after SCI was correlated with the chronic-stage GS. The ratios of lesion site λ_// to residual tissue λ_// and early-stage GS were predictive of the improvement in the PS at follow-up. Similarly, the ratios of lesion site λ_// to residual tissue λ_// and early-stage PS best predicted chronic GS recovery. Our findings demonstrate the predictive power of MRI combined with the early data-driven gait indexes for long-term outcomes. Such an approach may help clinicians to predict functional recovery accurately.     

Acute effects of cocaine on the neurobiology of cognitive control

Compromised ability to exert control over drug urges and drug-seeking behaviour is a characteristic of addiction. One specific cognitive control function, impulse control, has been shown to be a risk factor for the development of substance problems and has been linked in animal models to increased drug administration and relapse. We present evidence of a direct effect of cocaine on the neurobiology underlying impulse control. In a laboratory test of motor response inhibition, an intravenous cocaine administration improved task performance in 13 cocaine users. This improvement was accompanied by increased activation in right dorsolateral and inferior frontal cortex, regions considered critical for this cognitive function. Similarly, for both inhibitory control and action monitoring processes, cocaine normalized activation levels in lateral and medial prefrontal regions previously reported to be hypoactive in users relative to drug-naive controls. The acute amelioration of neurocognitive dysfunction may reflect a chronic dysregulation of those brain regions and the cognitive processes they subserve. Furthermore, the effects of cocaine on midline function suggest a dopaminergically mediated intersection between cocaine's acute reinforcing effects and its effects on cognitive control.     

Suitability of antral follicle counts and computer-assisted analysis of ultrasonographic and magnetic resonance images for estimating follicular reserve in porcine,ovine and bovine ovaries ex situ

This study was conducted to determine if correlations exist between the numbers of microscopic follicles comprising ovarian follicular reserve (OFR) and antral follicle counts (AFCs), and to assess the usefulness of computerized analyses of ovarian ultrasonograms and magnetic resonance (MR) images for estimating OFR in excised porcine, ovine and bovine ovaries. As a pre-requisite to these analyses, we characterized and compared ovarian cortical histomorhpology and follicle populations in the three species varying in prolificacy and overall reproductive longevity, and hence the total number of microscopic and antral follicles. Ultrasonographic and MR images were obtained at the scanner settings optimized to provide opposing contrasts between antral follicles and the ovarian stroma. Commercially available ImageProPlus® analytical software was used to calculate numerical pixel values (NPVs) and pixel heterogeneity (standard deviation of the pixel values) along the computer-generated lines (4–6) placed in the area corresponding to the ovarian cortex. The numbers of primordial (r = 0.38, P < 0.01) and intermediate follicles (r = 0.37, P < 0.01) were correlated with the numbers of antral follicles in bovine ovarian sections. The numbers of primordial (r = 0.28, P < 0.05), intermediate (r = 0.31, P < 0.01) and primary follicles (r = 0.27, P < 0.05) correlated directly with mean NPVs of the ultrasonographic ovarian images in cattle. There was a negative correlation between primary follicle numbers and NPVs of MR images (3D FAST-SPOILED GRADIENT ECHO) of the porcine ovarian cortex (r = −0.31, P < 0.05). To summarize, the numbers of primordial and intermediate follicles could only be estimated from AFCs in cows. Using ultrasound NPVs, the numbers of primordial, intermediate and primary follicles could be directly estimated in bovine ovaries and the quantitative image attributes of MR images were useful for quantifying porcine primary follicles. The bovine ovarian model is compatible with human situation and hence future studies should be undertaken to ascertain the usefulness of AFCs and ultrasonographic image analyses for estimating OFR in women.