IMPROVEMENT OF CHOLEDOCHOSCOPY: CHROMOENDOCHOLEDOCHOSCOPY,AUTOFLUORESCENCE IMAGING,OR NARROW‐BAND IMAGING

Past and present results concerning assessment of choledochoscopy using chromoendoscopy, autofluorescence imaging (AFI), or narrow‐band imaging (NBI) are summarized herein. On chromoendocholedochoscopy using methylene blue, cancer was stained dark blue. Interestingly, normal bile duct had dimple signs that are a significant feature of non‐neoplastic mucosa. First‐generation AFI (laser‐induced fluorescence endoscopy–gastrointestine system) and system of autofluorescence endoscopy made it possible to detect neoplastic lesions as dark green–black lesions, although the image was insufficient. The sensitivity, specificity and diagnostic accuracy of white light illumination and AFI were 88.0%, 87.5%, 87.7%, and 100%, 52.5%, 70.8%, respectively. In contrast, the recently developed NBI system made it possible to emphasize the imaging of certain features such as mucosal structures and mucosal microvessels. NBI showed not only clear neoplastic findings such as irregular mucosa or tortuous tumor vessel, but also non‐neoplastic findings such as smooth surface mucosa or dimple sign. In conclusion, the diagnostic power of chromoendoscopy and AFI were low, but NBI is expected to become the new‐generation diagnostic tool for biliary tract diseases.     

Site-specifically labeled CA19.9-targeted immunoconjugates for the PET,NIRF, and multimodal PET/NIRF imaging of pancreatic cancer

Molecular imaging agents for preoperative positron emission tomography (PET) and near-infrared fluorescent (NIRF)-guided delineation of surgical margins could greatly enhance the diagnosis, staging, and resection of pancreatic cancer. PET and NIRF optical imaging offer complementary clinical applications, enabling the noninvasive whole-body imaging to localize disease and identification of tumor margins during surgery, respectively. We report the development of PET, NIRF, and dual-modal (PET/NIRF) imaging agents, using 5B1, a fully human monoclonal antibody that targets CA19.9, a well-established pancreatic cancer biomarker. Desferrioxamine (DFO) and/or a NIRF dye (FL) were conjugated to the heavy-chain glycans of 5B1, using a robust and reproducible site-specific (ss) labeling methodology to generate three constructs (^ssDFO-5B1, ^ssFL-5B1, and ^ssdual-5B1) in which the immunoreactivity was not affected by the conjugation of either label. Each construct was evaluated in a s.c. xenograft model, using CA19.9-positive (BxPC3) and -negative (MIAPaCa-2) human pancreatic cancer cell lines. Each construct showed exceptional uptake and contrast in antigen-positive tumors with negligible nonspecific uptake in antigen-negative tumors. Additionally, the dual-modal construct was evaluated in an orthotopic murine pancreatic cancer model, using the human pancreatic cancer cell line, Suit-2. The ^ssdual-5B1 demonstrated a remarkable capacity to delineate metastases and to map the sentinel lymph nodes via tandem PET-computed tomography (PET/CT) and NIRF imaging. Fluorescence microscopy, histopathology, and autoradiography were performed on representative sections of excised tumors to visualize the distribution of the constructs within the tumors. These imaging tools have tremendous potential for further preclinical research and for clinical translation.Pancreatic ductal adenocarcinoma (PDAC) is currently the fourth leading cause of cancer mortality and is expected to surpass both colorectal and breast cancer in total annual deaths by 2030 (1, 2). Surgical resection of the pancreas is the only curative treatment, but the presence of metastases precludes over 80% of patients from resection ab initio (3). The overall 5-y survival rate is ∼5%, and for those who qualify for surgical resection, the 5-y survival rate is only 25% due to the high incidence of undiscovered metastases (4, 5). Further complicating this dire situation, patients with PDAC are regularly misdiagnosed or understaged, confounding treatment strategies and preventing proper enrollment in clinical trials. Many of these problems could be avoided and outcomes improved if adequate clinical tools for diagnosing, staging, and treating PDAC were available.Positron emission tomography (PET) is a promising technological platform for detecting, staging, and monitoring the progression or regression of many solid tumors, including PDAC. Optical imaging is a complementary platform that makes possible the accurate identification of tumor tissue in an intraoperative setting, which was recently demonstrated in human patients with ovarian cancer (6). Currently, the only Food and Drug Administration approved imaging agent for PDAC is 2-deoxy-2-[¹⁸F]-fluoro-D-glucose (FDG). FDG PET imaging relies on increased tumor metabolism relative to nonmalignant cells (Warburg effect) (7). However, FDG has numerous shortcomings when it comes to PDAC, including unreliable detection of small primary lesions (<7 mm) (8) or liver metastases (<1 cm) (9), an inherent inability to discriminate between benign disease (i.e., pancreatitis) and malignancy (10), and decreased tumor avidity for FDG upon chemo- or radiation therapy (11). The development of an arsenal of imaging tools, particularly a dual-modal imaging agent that seamlessly incorporates the advantages of both PET and optical imaging, could definitively improve the outcomes in patients with PDAC.Monoclonal antibodies (mAbs) can provide the necessary specificity, sensitivity, and flexibility for the development of such tools. PET imaging with a radiolabeled mAb (immunoPET) would enhance our ability to noninvasively detect small lesions and slowly growing epithelial cancers (12–14). Near-infrared fluorescent (NIRF) dyes are particularly attractive in intraoperative applications because they show good tissue penetration (up to 1 cm) and low background from autofluorescence. Optical imaging with a NIRF-labeled mAb would allow surgeons to precisely identify tumor margins during resection, ensuring minimal healthy tissue is removed and that no residual tumor tissue is overlooked. Technological advancements in the clinic are now at a stage that allows clinical translation into humans, providing renewed impetus for the preclinical development of tools for NIRF imaging (15, 16).CA19.9 (also known as sialyl Lewis^a) is a ligand for epithelial leukocyte adhesion molecules, and its overexpression is a key event in invasion and metastasis of many cancers, including PDAC (17). CA19.9 is an attractive target for imaging of PDAC because it is the most highly expressed tumor antigen (18, 19) and is minimally expressed in healthy pancreas tissue (20). In fact, the diagnosis of PDAC is often aided by the detection of elevated levels of circulating CA19.9 (21, 22). The promise of CA19.9 as a biomarker of PDAC led to the initiation of several antibody discovery programs (14, 20, 23) and the development of the fully human mAb 5B1, which binds an extracellular epitope of CA19.9 with low nanomolar affinity (23). Recently, we demonstrated that CA19.9 could serve as a target for immunoPET imaging of PDAC, even in the context of circulating antigen (24). Based on those results, we set out to improve and expand upon the usefulness of 5B1 in the context of PDAC imaging.The canonical methodology for the development of mAbs for PET and/or optical imaging suffers from several shortcomings that are a consequence of the indiscriminate conjugation of chelators or dyes to nucleophilic amino acids. Those shortcomings include the loss of immunoreactivity due to conjugation at the antigen-binding region, random conjugation that leads to poorly defined constructs, and an intrinsic lack of reproducibility, as well as laborious, costly optimization of each novel construct. The combination of glycan engineering and bioorthogonal “click” chemistry has proved a successful strategy for conjugating molecules distal to the antigen-binding region of mAbs in a manner that is highly specific and reproducible, circumventing the aforementioned problems (25, 26). Specifically, using a site-specific conjugation strategy for affixing chelator and/or dye molecules via the heavy chain glycans leads to well-defined, robust immunoconjugates in a highly reproducible manner that requires minimal optimization and results in a minimal loss of immunoreactivity. Furthermore, conjugation via the heavy chain glycans offers an exceptional opportunity to construct site-specific, dual-modal immunoconjugates, which are otherwise challenging to develop using traditional conjugation methodology.Herein, we describe the development of three distinct immunoconjugates that were site-specifically conjugated with DFO for radiolabeling with ⁸⁹Zr and PET imaging, a NIRF dye for optical imaging, or a dual-labeled construct with both DFO and NIRF dye combining the advantages of PET and NIRF into a single construct. Using the site-specific, bioorthogonal conjugation strategy produced well-defined constructs that retained high levels of immunoreactivity compared with their nonspecifically labeled counterparts. The dual-labeled 5B1 construct, in particular, showed excellent uptake in murine models of PDAC, including delineation of small metastases and dissemination of antigen to sentinel lymph nodes in an orthotopic model.     

British Society for Haematology, Slide session, Annual Scientific Meeting, Bournemouth, 2007

Eight cases discussed by experts at the 2007 Annual Scientific Meeting of the British Society of Haematology are presented as at the meeting, with a discussion of the morphological features, digital information and differential diagnosis being followed by further information and a final diagnosis. Additionally, digital slides of two of the cases were available to be viewed by the internet with the opportunity for delegates to suggest diagnoses.     

British Society for Haematology,slide session,annual scientific meeting,Glasgow, 2008

A morphology session is held each year at the Annual Scientific Meeting of the British Society of Haematology. Prior to the meeting this year, eight morphology cases were made available to BSH members as glass slides and also digitally as ‘virtual slides’. A panel of invited commentators who had no prior knowledge of the diagnosis discussed the eight cases. An initial limited history and blood count are given with representative images from the case material; this is followed by the discussants’ comments and suggested diagnosis. The actual clinical diagnosis is then given with other relevant information.     

Intraoperative epicardial coronary artery imaging: rationale,methods, and applications

Epicardial coronary imaging using high frequency (7-12 MHz) ultrasound probes could aid the surgeon performing coronary artery bypass procedures by localizing the coronary artery segments underneath epicardial fat, identifying the site of coronary stenosis to be bypassed, evaluating the integrity of distal coronary artery, assessing the efficacy of anastomosis, and detecting anastomotic complications. While an ideal coronary imaging probe is yet to be developed, early clinical experience with vascular imaging probes applied on the coronary vessels suggests that epicardial coronary artery imaging could enhance the optimum performance of coronary interventions. Fabrication of a flexible high frequency probe that could be applied not only on the arteries on the anterior surface of the heart but also on the lateral and posterior surfaces could facilitate development of newer surgical procedures as well.     

Colorectal cancer: Parametric evaluation of morphological,functional and molecular tomographic imaging

Colorectal cancer(CRC) represents one of the leading causes of tumor-related deaths worldwide. Among the various tools at physicians' disposal for the diagnostic management of the disease, tomographic imaging(e.g., CT, MRI, and hybrid PET imaging) is considered essential. The qualitative and subjective evaluation of tomographic images is the main approach used to obtain valuable clinical information, although this strategy suffers from both intrinsic and operator-dependent limitations. More recently, advanced imaging techniques have been developed with the aim of overcoming these issues. Such techniques,such as diffusion-weighted MRI and perfusion imaging, were designed for the"in vivo" evaluation of specific biological tissue features in order to describe them in terms of quantitative parameters, which could answer questions difficult to address with conventional imaging alone(e.g., questions related to tissue characterization and prognosis). Furthermore, it has been observed that a large amount of numerical and statistical information is buried inside tomographic images, resulting in their invisibility during conventional assessment. This information can be extracted and represented in terms of quantitative parameters through different processes(e.g., texture analysis). Numerous researchers have focused their work on the significance of these quantitative imaging parameters for the management of CRC patients. In this review, we aimed to focus on evidence reported in the academic literature regarding the application of parametric imaging to the diagnosis, staging and prognosis of CRC while discussing future perspectives and present limitations. While the transition frompurely anatomical to quantitative tomographic imaging appears achievable for CRC diagnostics, some essential milestones, such as scanning and analysis standardization and the definition of robust cut-off values, must be achieved before quantitative tomographic imaging can be incorporated into daily clinical practice.     

Texture and color enhancement imaging for detecting colorectal adenomas: Good,but not good enough

Texture and color enhancement imaging (TXI) has been developed as a novel image-enhancing endoscopy. However, the effectiveness of TXI detecting adenomas is inferior to narrow band imaging. Thus, future studies will need to focus on investigating the feasibility of such combination in clinical settings in order to provide patients with more accurate diagnoses.     

Multiparametric or practical quantitative liver MRI: towards millisecond,fat fraction,kilopascal and function era

Introduction: New advances in liver magnetic resonance imaging (MRI) may enable diagnosis of unseen pathologies by conventional techniques. Normal T1 (550–620 ms for 1.5 T and 700–850 ms for 3 T), T2, T2* (>20 ms), T1rho (40–50 ms) mapping, proton density fat fraction (PDFF) (≤5%) and stiffness (2-3kPa) values can enable differentiation of a normal liver from chronic liver and diffuse diseases. Gd-EOB-DTPA can enable assessment of liver function by using postcontrast hepatobiliary phase or T1 reduction rate (normally above 60%). T1 mapping can be important for the assessment of fibrosis, amyloidosis and copper overload. T1rho mapping is promising for the assessment of liver collagen deposition. PDFF can allow objective treatment assessment in NAFLD and NASH patients. T2 and T2* are used for iron overload determination. MR fingerprinting may enable single slice acquisition and easy implementation of multiparametric MRI and follow-up of patients.

Areas covered: T1, T2, T2*, PDFF and stiffness, diffusion weighted imaging, intravoxel incoherent motion imaging (ADC, D, D* and f values) and function analysis are reviewed.

Expert commentary: Multiparametric MRI can enable biopsyless diagnosis and more objective staging of diffuse liver disease, cirrhosis and predisposing diseases. A comprehensive approach is needed to understand and overcome the effects of iron, fat, fibrosis, edema, inflammation and copper on MR relaxometry values in diffuse liver disease.     

Melatonin and the human hippocampus, a time dependent interplay

Melatonin serves as a signal of darkness and participates in sleep/wake regulation. Animal studies demonstrated effects of melatonin in the hippocampus, particularly suggesting involvement in synaptic plasticity. We used functional magnetic resonance imaging to identify and investigate effects of melatonin in the human hippocampus. Activity in the hippocampal complex during a memory task was examined at 22:00 hr (when endogenous melatonin levels are normally increasing) and compared with 16:00 hr (when endogenous melatonin levels are minimal). The relationship between observed activation patterns and endogenous melatonin was assessed. Finally, the effects of exogenous melatonin administered at 22:00 hr were studied in a double-blind, placebo-controlled crossover manner. Our findings indicate that activation in the left hippocampus at 22:00 hr is significantly reduced compared with afternoon hours compatible with diurnal variation in hippocampal activity. Exogenous melatonin further reduced activation in this region, only in subjects who already crossed the melatonin onset phase at this hour and in correlation with endogenous melatonin levels. As such an effect was not demonstrated with afternoon administration of melatonin, a time depended effect is suggested. Contrary, activation in the left para-hippocampus at 22:00 hr was higher in subjects that crossed the melatonin onset phase. Parahippocampal activation correlated with individual endogenous melatonin levels and was not further affected by exogenous melatonin. These results demonstrate that memory related activation in the hippocampus and para-hippocampus are affected by time of day and melatonin in a differential manner and may implicate the circadian clock and melatonin in human memory processing during the night.     

Imaging in rheumatoid arthritis – status and recent advances for magnetic resonance imaging, ultrasonography, computed tomography and conventional radiography

Within the field of imaging in RA, large and exciting advances have been made during the last decade. Although X-ray is still the most widely used tool for monitoring disease progression, other methods offer clear advantages through more sensitive depiction of inflammatory and destructive disease manifestations. MRI and US are increasingly used in RA trials and practice. MRI can visualize all the features involved in inflammation and damage in RA patients, and have documented independent prognostic value and superior sensitivity to change compared with conventional methods. US offers sensitive assessment of joint damage and, particularly, inflammation, and can be used by practising rheumatologists as part of the clinical examination. CT provides high-resolution images of erosion, and may have potential for sensitive monitoring of erosive progression.Overall, these new imaging modalities already provide important benefits for the clinician, including: more sensitive detection of early disease manifestations; more sensitive monitoring of responses to therapeutic agents, including improved assessment of whether optimal disease control (remission) has been achieved; and improved prognostication. Many questions concerning the optimal use of these new imaging modalities require further research efforts, but as technical advances are still progressing rapidly, the clinical and research applications of these modern imaging modalities are also expected to increase markedly during the next decade.Imaging could be useful in practice for the following:

A. In routine clinical practice

• to establish a diagnosis of RA (ACR 1987 criteria): X-ray

• to assist with the diagnostic workout in suspected, but not definite, inflammatory joint disease and early, unclassified inflammatory joint disease (by detection of presence/absence of synovitis, enthesitis, bone erosions etc.): MRI, US

• to monitor structural joint damage: X-ray, MRI

• to monitor disease activity: MRI, US

• to assist with the prognostic stratification of patients with early RA: X-ray, MRI

• to help define the presence or absence of true remission: MRI, US

• to guide aspirations and injections in joints, bursae and tendon sheaths: US

B. In research

• to assess structural joint damage in phase III/IV RA trials: X-ray, MRI

• to assess the anti-inflammatory effectiveness of a new compound (‘proof of concept' studies): MRI, US

• for pretrial selection of the patients most likely to progress (‘enrichment'): X-ray, MRI

For the individual imaging modalities, further exploration of:

• clinical value of differential diagnosis in early and in early suspected, but not certain, inflammatory joint disease: MRI, US

• clinical value of monitoring disease activity by imaging: MRI, US

• defining imaging remission and/or an imaging ‘acceptable state’: MRI, US

• clinical value of monitoring joint damage by imaging: MRI, US, CT

• benefit of and optimal methods for using modern imaging in clinical trials: MRI, US, CT

• development and testing of new technical methods: US (e.g. three-dimensional, new transducers), MRI (e.g. 3 Tesla imaging, whole-body MRI), X-ray (e.g. software for automated image interpretation)

Solid MRI contrast agents for long-term,quantitative in vivo oxygen sensing

Targeted MRI contrast agents have proven useful in research and clinical studies for highlighting specific metabolites and biomarkers [Davies GL, et al. (2013) Chem Commun (Camb) 49(84):9704–9721] but their applicability in serial imaging is limited owing to a changing concentration postinjection. Solid enclosures have previously been used to keep the local concentration of contrast agent constant, but the need to surgically implant these devices limits their use [Daniel K, et al. (2009) Biosens Bioelectron 24(11):3252–3257]. This paper describes a novel class of contrast agent that comprises a responsive material for contrast generation and an injectable polymeric matrix for structural support. Using this principle, we have designed a contrast agent sensitive to oxygen, which is composed of dodecamethylpentasiloxane as the responsive material and polydimethylsiloxane as the matrix material. A rodent inspired-gas model demonstrated that these materials are functionally stable in vivo for at least 1 mo, which represents an order of magnitude improvement over an injection of liquid siloxane [Kodibagkar VD, et al. (2006) Magn Reson Med 55(4):743–748]. We also observed minimal adverse tissue reactions or migration of contrast agents from the initial injection site. This class of contrast agents, thus, represented a new and complementary method to monitor chronic diseases by MRI.MRI is one of the most important clinical technologies for monitoring disease progression and is unique among imaging modalities in its ability to gather both high-resolution anatomical images and physiological information in the same study (1). Targeted contrast agents are useful for highlighting specific molecules in the body (2), whereas responsive contrast agents enable quantitative diagnostics using MRI. The concentration of contrast agents decreases over time owing to systemic clearance (3); some magnetic resonance (MR) methods, such as dynamic contrast-enhanced imaging, exploit this clearance of contrast agent to make inferences about the underlying physiology. Some applications, however, require a consistent concentration of contrast agent for repeatable, accurate, and quantitative measurements (4), and an internal control must be added to account for the time-changing concentration. Repeat measurements to track the progression of disease or the response to treatment also require a new bolus injection of contrast agent. These additional injections introduce uncertainty in the measurements, and the safety of long-term exposure to the contrast agent must be investigated. We describe a novel solid contrast agent that eliminates these issues to enable longitudinal imaging sensitive to oxygen. It consists of a contrast agent embedded in an injectable polymeric matrix where the matrix ensures the retention of sensitive agents in the target tissue for extended periods of time. We believe that these agents will find use in clinical medicine by enabling quantitative measurements of specific local metabolites in chronic conditions.One area where longitudinal imaging can affect clinical decision making is sensing of local oxygen tension. Oxygen plays an important role in many pathological processes, such as cancer (5), peripheral vascular disease (6), and wound healing (7). Oxygen delivery in cancer can be limited transiently by perfusion interruption or chronically by increases in diffusion distance (8); both of these mechanisms result in hypoxia. Hypoxia in cancer confers resistance to radiotherapy (9, 10), impedes the action of chemotherapeutic agents (11), and promotes metastasis (12). Recent studies have attributed the low efficacy of drugs designed to target hypoxia to the lack of a suitable companion diagnostic assay (13–15). A diagnostic assay for selecting appropriate patients for hypoxia-targeted treatment or doses for radiotherapy would need to report oxygen status in the tumor at multiple time points during the course of treatment, because the tumor oxygen tension is dynamic and changes in response to treatment (16). There is a need for an oxygen assay that can provide oxygen information in the same location so that follow-up data can be used to evaluate treatment efficacy. Earlier attempts to measure oxygen with polarographic needle oxygen electrodes provided important evidence of hypoxia in human tumors, but oxygen electrodes have limited clinical applications owing to the invasiveness of the measurement procedure (17). Technologies currently used in the clinic for monitoring oxygen are only useful in areas with sufficient blood flow [pulse oximetry (18)], that are close to the surface [transcutaneous oximetry (19)], or that have limited changes in oxygen tension [fiber optic probes (15)]. Magnetic resonance methods, such as electron paramagnetic resonance (20) and ¹⁹F oximetry (21), provide direct measurement of local oxygen tension but require specialized equipment not currently present in most medical centers. Other MR technologies, such as blood-oxygen-level-dependent and tissue-oxygen-level-dependent contrast imaging, are qualitative in nature and do not report absolute tissue oxygen tension (15, 22).MRI contrast agents are compatible with existing equipment in the clinic, but the clearance of the contrast agent prohibits long-term monitoring. Several technologies have previously been developed to compensate for variations in contrast agent concentration (23). These methods typically require measurement of multiple parameters or established perfusion models to compensate for the concentration changes (24). Our matrix-embedded contrast agent performs measurements independently of perfusion, is not cleared, and shows no loss in performance after 1 mo in vivo.     

早产儿脑白质损伤早期MRI-DWI的分类、演变及临床意义

目的结合常规MRI和弥散加权成像（DWI）探讨早产儿脑白质损伤（CWMD）的较客观分类方法,动态评价不同类型CWMD的变化规律及临床意义。方法 517例早产儿行常规MRI和DWI检查,确诊早产儿CWMD212例,对其中55例随访。结果随病变累及区域数目不同,异常信号有特征性分布及形态学改变,呈现一系列动态变化,并与神经发育结局有较好的相关性。根据早期CWMD类型可以预测后期发生脑室周围白质软化（PVL）的类型,反之根据PVL类型可以推测早期CWMD类型。早期（1周内）DWI能提早发现病变,在一定程度上预示预后。常规MRI晚期（3周左右）检查能高度预测患儿预后。结论常规MRI和DWI相结合可动态观察CWMD病变受累区域,与形态学相结合可较客观评价患者预后,并对高危早产儿进行早期合理康复。     

Cloaked electromagnetic, acoustic, and quantum amplifiers via transformation optics

The advent of transformation optics and metamaterials has made possible devices producing extreme effects on wave propagation. Here we describe a class of invisible reservoirs and amplifiers for waves, which we refer to as Schrödinger hats. The unifying mathematical principle on which these are based admits such devices for any time harmonic waves modeled by either the Helmholtz or Schrödinger equation, e.g., polarized waves in electromagnetism, acoustical waves and matter waves in quantum mechanics. Schrödinger hats occupy one part of a parameter-space continuum of wave-manipulating structures which also contains standard transformation optics based cloaks, resonant cloaks and cloaked sensors. Possible applications include near-field quantum microscopy.     

User-friendly and low-cost computer system for immediate review,analysis, and reconstruction of intracoronary ultrasound images

Rapid review, digital recording, on-line quantification, and three-dimensional reconstruction are all essential in the evaluation of intracoronary ultrasound images during coronary interventions. We describe a low-cost method that offers all these necessary features. The proposed method uses the QuickTime compatible video digitizers of standard multimedia Apple Macintosh or PowerPC desktop computers and the freeware software Object Image 1.60. Cathet. Cardiovasc. Diagn. 43:357–362, 1998. © 1998 Wiley-Liss, Inc.     

Functional MRI,Drugs, and Poststroke Recovery

Stroke is the first cause of disability in industrialized countries. Thus, understanding the mechanisms of poststroke recovery appears to be crucial in improving motor performance and reducing disability in stroke patients. Strategies through which brain restores lost functions after ischemic lesions are numerous. The mechanisms underlying poststroke recovery, known as cerebral plasticity, are so far hypothetical. However, functional magnetic resonance imaging (fMRI) studies recently have provided new insights in to stroke recovery. This article sketches out the mechanisms that are thought to underly recovery and focuses on fMRI experimental studies that have investigated the influence of a number of drugs on functional recovery. Functional MRI is a valuable tool in understanding functional recovery and may help to disclose new therapeutical approaches.     

Low-dose,simple, and fast grating-based X-ray phase-contrast imaging

Phase sensitive X-ray imaging methods can provide substantially increased contrast over conventional absorption-based imaging and therefore new and otherwise inaccessible information. The use of gratings as optical elements in hard X-ray phase imaging overcomes some of the problems that have impaired the wider use of phase contrast in X-ray radiography and tomography. So far, to separate the phase information from other contributions detected with a grating interferometer, a phase-stepping approach has been considered, which implies the acquisition of multiple radiographic projections. Here we present an innovative, highly sensitive X-ray tomographic phase-contrast imaging approach based on grating interferometry, which extracts the phase-contrast signal without the need of phase stepping. Compared to the existing phase-stepping approach, the main advantages of this new method dubbed “reverse projection” are not only the significantly reduced delivered dose, without the degradation of the image quality, but also the much higher efficiency. The new technique sets the prerequisites for future fast and low-dose phase-contrast imaging methods, fundamental for imaging biological specimens and in vivo studies.