Intramembrane client recognition potentiates the chaperone functions of calnexin.

One-third of the human proteome is comprised of membrane proteins, which are particularly vulnerable to misfolding and often require folding assistance by molecular chaperones. Calnexin (CNX), which engages client proteins via its sugar-binding lectin domain, is one of the most abundant ER chaperones, and plays an important role in membrane protein biogenesis. Based on mass spectrometric analyses, we here show that calnexin interacts with a large number of nonglycosylated membrane proteins, indicative of additional nonlectin binding modes. We find that calnexin preferentially bind misfolded membrane proteins and that it uses its single transmembrane domain (TMD) for client recognition. Combining experimental and computational approaches, we systematically dissect signatures for intramembrane client recognition by calnexin, and identify sequence motifs within the calnexin TMD region that mediate client binding. Building on this, we show that intramembrane client binding potentiates the chaperone functions of calnexin. Together, these data reveal a widespread role of calnexin client recognition in the lipid bilayer, which synergizes with its established lectin-based substrate binding. Molecular chaperones thus can combine different interaction modes to support the biogenesis of the diverse eukaryotic membrane proteome.

PET/CTA detection of muscle inflammation related to cholesterol crystal emboli without arterial obstruction.

BACKGROUND: PET/CTA was used to evaluate the effect of cholesterol crystal emboli (CCE) on muscle injury. Cholesterol crystals (CCs) released during plaque rupture travel downstream and lodge in muscle triggering inflammation and tissue injury. METHODS: Thigh muscles in three groups of rabbits (n = 22) were studied after intra-arterial injection of CCs, Group I (n = 10); polystyrene microspheres, Group II (n = 5); or normal saline, Group III (n = 7). After 48 hours, muscle inflammation and injury were measured by fluorodeoxy-glucose uptake using PET/CTA, serum tissue factor (TF), and creatinine phosphokinase (CPK). Macrophages were stained with RAM11 and CCs with Bodipy. RESULTS: SUVmax of thigh muscles was greater for Group I vs Group II and III (0.40 ± 0.16 vs 0.21 ± 0.11, P = .038 and 0.23 ± 0.06, P = .036). CPK levels rose significantly in Group I vs Group II and III (6.7 ± 6.0 vs 0.6 ± 0.4, P = .007 and 0.9 ± 0.4 mg·dL-1, P = .023). No arterial thrombosis was detected by CTA or histology of embolized arteries and TF did not rise significantly. There were extensive macrophage infiltrates surrounding muscle necrosis in Group I only. CONCLUSIONS: Cholesterol crystal emboli triggered muscle inflammation and necrosis with an intact circulation. PET/CTA may help in the early detection of inflammation caused by CCs.

Characterisation of Large-Sized REBaCuO Bulks for Application in Flux Modulation Machines.

High temperature superconductors (HTSs) are enablers of extensive electrification for aircraft propulsion. Indeed, if used in electrical machines, HTS materials can drastically improve their performance in terms of the power-to-weight ratio. Among the different topologies of superconducting electrical machines, a flux modulation machine based on HTS bulks is of interest for its compactness and light weight. Such a machine is proposed in the FROST (Flux-barrier Rotating Superconducting Topology) project led by Airbus to develop new technologies as part of their decarbonization goals driven by international policies. The rotor of the machine will house large ring-segment-shaped HTS bulks in order to increase the output power. However, the properties of those bulks are scarcely known and have barely been investigated in the literature. In this context, the present work aims to fill out partially this scarcity within the framework of FROST. Thus, a thorough characterisation of the performances and homogeneity of 11 large REBaCuO bulks was carried out. Ten of the bulks are to be utilized in the machine prototype, originally keeping the eleventh bulk as a spare. A first set of characterisation was conducted on the eleven bulks. For this set, the trapped field mapping and the critical current were estimated. Then, a series of in-depth characterisations on the eleventh bulk followed. It included critical current measurement, X-ray diffraction, and scanning electron microscopy on different millimetre-size samples cut out from the bulk at various locations. The X-ray diffraction and scanning electron microscopy showed weakly oxygenated regions inside the bulk explaining the local drop or loss in superconducting properties. The objective was to determine the causes of the inhomogeneities found in the trapped field measured on all the bulks, sacrificing one of them, here the spare one. To help obtain a clearer picture, a numerical model was then elaborated to reproduce the field map of the eleventh bulk using the experimental data obtained from the characterisation of its various small samples. It is concluded that further characterisations, including the statistics on various bulks, are still needed to understand the underlying reasons for inhomogeneity in the trapped field. Nonetheless, all the bulks presented enough current density to be usable in the construction of the proposed machine.

Evaluation of hypoxia in a feline model of head and neck cancer using 64Cu-ATSM positron emission tomography/computed tomography.

BACKGROUND: Human and feline head and neck squamous cell carcinoma (HNSCC) share histology, certain molecular features, as well as locally aggressive and highly recurrent clinical behavior. In human HNSCC, the presence of significant hypoxia within these tumors is considered an important factor in the development of a more aggressive phenotype and poor response to therapy. We hypothesized that feline head and neck tumors, particularly HNSCC, would exhibit hypoxia and that 64Cu-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM) positron emission tomography/computed tomography (PET/CT) would permit detection of intratumoral hypoxia. METHODS: 12 cats with measureable head and neck tumors were given 64Cu-ATSM and iodinated contrast for PET/CT scan. The presence or absence of hypoxia was also assessed using an intratumoral fluorescent life-time probe to quantitate pO2 and pimonidazole immunohistochemical staining in biopsy specimens. In two cats, intratumoral O2 and 64Cu-ATSM uptake was measured before and after treatment with anti-angiogenic agents to determine the effect of these agents on hypoxia. RESULTS: Eleven of twelve feline tumors demonstrated significant 64Cu-ATSM uptake, regardless of malignant or benign etiology. The presence (and absence) of hypoxia was confirmed using the fluorescent O2 detection probe in nine tumors, and using pimonidazole staining in three tumors. Squamous cell carcinomas (HNSCC) demonstrated the highest degree of hypoxia, with Tmax/M ratios ranging from 4.3 to 21.8. Additional non-neoplastic tissues exhibited 64Cu-ATSM uptake suggestive of hypoxia including reactive draining lymph nodes, non-malignant thyroid pathology, a tooth root abscess, and otitis media. In two cats with HNSCC that received anti-vascular agents, the pattern of 64Cu-ATSM uptake was altered after treatment, demonstrating the potential of the feline model to study the modulation of tumor oxygenation. CONCLUSION: Feline HNSCC serves as a clinically relevant model for the investigation of intratumoral hypoxia including its measurement, modulation and targeting.

Mechanistic insights into the aggregation pathway of the patient-derived immunoglobulin light chain variable domain protein FOR005.

Systemic antibody light chain (AL) amyloidosis is characterized by deposition of amyloid fibrils. Prior to fibril formation, soluble oligomeric AL protein has a direct cytotoxic effect on cardiomyocytes. We focus on the patient derived λ-III AL variable domain FOR005 which is mutated at five positions with respect to the closest germline protein. Using solution-state NMR spectroscopy, we follow the individual steps involved in protein misfolding from the native to the amyloid fibril state. Unfavorable mutations in the complementary determining regions introduce a strain in the native protein structure which yields partial unfolding. Driven by electrostatic interactions, the protein converts into a high molecular weight, oligomeric, molten globule. The high local concentration of aggregation prone regions in the oligomer finally catalyzes the conversion into fibrils. The topology is determined by balanced electrostatic interactions in the fibril core implying a 180° rotational switch of the beta-sheets around the conserved disulfide bond.

A chemical probe unravels the reactive proteome of health-associated catechols.

Catechol-containing natural products are common constituents of foods, drinks, and drugs. Natural products carrying this motif are often associated with beneficial biological effects such as anticancer activity and neuroprotection. However, the molecular mode of action behind these properties is poorly understood. Here, we apply a mass spectrometry-based competitive chemical proteomics approach to elucidate the target scope of catechol-containing bioactive molecules from diverse foods and drugs. Inspired by the protein reactivity of catecholamine neurotransmitters, we designed and synthesised a broadly reactive minimalist catechol chemical probe based on dopamine. Initial labelling experiments in live human cells demonstrated broad protein binding by the probe, which was largely outcompeted by its parent compound dopamine. Next, we investigated the competition profile of a selection of biologically relevant catechol-containing substances. With this approach, we characterised the protein reactivity and the target scope of dopamine and ten biologically relevant catechols. Strikingly, proteins associated with the endoplasmic reticulum (ER) were among the main targets. ER stress assays in the presence of reactive catechols revealed an activation of the unfolded protein response (UPR). The UPR is highly relevant in oncology and cellular resilience, which may provide an explanation of the health-promoting effects attributed to many catechol-containing natural products.

Disruption of limbic white matter pathways in mild cognitive impairment and Alzheimer's disease: a DTI/FDG-PET study.

BACKGROUND: Alzheimer's disease (AD) and mild cognitive impairment (MCI) affect the limbic system, causing medial temporal lobe (MTL) atrophy and posterior cingulate cortex (PCC) hypometabolism. Additionally, diffusion tensor imaging (DTI) studies have demonstrated that MCI and AD involve alterations in cerebral white matter (WM) integrity. OBJECTIVES: To test if (1) patients with MCI and AD exhibit decreases in the integrity of limbic WM pathways; (2) disconnection between PCC and MTL, manifested as disruption of the cingulum bundle, contributes to PCC hypometabolism during incipient AD. METHODS: We measured fractional anisotropy (FA) and volume of the fornix and cingulum using DTI in 23 individuals with MCI, 21 with mild-to-moderate AD, and 16 normal control (NC) subjects. We also measured PCC metabolism using (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) in AD and MCI patients. RESULTS: Fornix FA and volume were reduced in MCI and AD to a similar extent. Descending cingulum FA was reduced in AD while volume was reduced in MCI and even more so in AD. Both FA and volume of the fornix and descending cingulum reliably discriminated between NC and AD. Fornix FA and descending cingulum volume also reliably discriminated between NC and MCI. Only descending cingulum volume reliably discriminated between MCI and AD. In the combined MCI-AD cohort, PCC metabolism directly correlated with both FA and volume of the descending cingulum. CONCLUSIONS: Disruption of limbic WM pathways is evident during both MCI and AD. Disconnection of the PCC from MTL at the cingulum bundle contributes to PCC hypometabolism during incipient AD.

Plaque rupture and thrombosis are reduced by lowering cholesterol levels and crystallization with ezetimibe and are correlated with fluorodeoxyglucose positron emission tomography.

OBJECTIVE: This study evaluated effects of lipid lowering with ezetimibe on plaque burden and associated cholesterol crystallization and inflammation in a rabbit model of plaque disruption and thrombosis. METHODS AND RESULTS: Atherosclerotic rabbits (Group I, n=10 without; Group II, n=12 with ezetimibe, 1 mg/kg per day) were pharmacologically triggered for plaque disruption. Fluorodeoxyglucose positron emission tomography, RAM 11 macrophage staining, and serum inflammatory markers detected arterial inflammation. Serum and aortic wall cholesterol levels were measured, and thrombus area was planimetered. Cholesterol crystal density on aortic surface was scored (0 to +3) by scanning electron microscopy. Serum and aortic wall cholesterol, plaque area, and thrombosis area were significantly lower in Group II versus Group I (83.4±106.4 versus 608±386 mg/dL, P=0.002; 3.12±1.40 versus 9.39±5.60 mg/g, P=0.003; 10.84±1.6 versus 17.48±1.8 mm(2), P<0.001; and 0.05±0.15 versus 0.72±0.58 mm(2), P=0.01, respectively). There were significant correlations between crystal density and plaque area (r=0.75, P<0.003) and between crystal density and RAM 11 (r=0.82, P<0.001). Scanning electron microscopy demonstrated that there were fewer crystals in Group II versus Group I (+1.2±0.61 versus +2.4±0.63, P<0.001) and less inflammation detected by fluorodeoxyglucose positron emission tomography and RAM 11 (P<0.004 and P<0.04, respectively). CONCLUSIONS: Lowering cholesterol levels with ezetimibe reduced plaque burden, crystallization, and inflammation, preventing plaque disruption and thrombosis.

Do brain activation changes persist in athletes with a history of multiple concussions who are asymptomatic?

PRIMARY OBJECTIVE: To evaluate brain activation patterns of asymptomatic athletes with a history of two or more concussions. RESEARCH DESIGN: A paired case-control design was used to evaluate brain activation patterns during cognitive performance in 14 athletes with a history of two or more concussions and 14 age- and sex-matched controls with no previous concussion. METHODS AND PROCEDURES: Percentage Blood-Oxygen-Level-Dependent (BOLD) change during an N-back working memory task was assessed in all participants. Performance on the Trail-Making Test Form A and B, Symbol-Digit Modalities Test and the Immediate Post-concussion Assessment and Cognitive Test (ImPACT) was also compared between groups. MAIN RESULTS: As expected, brain regions activated during the performance of the N-back were equivalent between groups. The groups performed similarly on the neurocognitive measures. The history of concussion group was less accurate than controls on the 1-, 2- and 3-back conditions of the N-back. CONCLUSIONS: Following the complete resolution of symptoms, a history of two or more concussions is not associated with changes in regional brain activation during the performance of working memory task. Compensatory brain activation may only persist during the typically brief time athletes experience symptoms following concussion.

"If We Build It, Will They Come?" A Cohort Study of Family Utilization of a Pediatric-Specific Hospice Home.

Objective: To determine whether families would make use of a pediatric-specific inpatient hospice facility for end-of-life care for children. Background: Location of end-of-life care and death are important considerations when treating children with life-limiting conditions. There is very limited research on utilization of an inpatient hospice facility for end-of-life care if a pediatric-specific facility is available. We examined changes in family utilization of inpatient hospice services with the availability of an inpatient pediatric hospice facility (PHF). Methods: We conducted a retrospective cohort study with data collected on location of end-of-life care and death five years prior to and five years following the opening of a PHF that receives referrals from a large children s hospital in United States. Two data sources from the hospice organization were used: (1) a dataset on origins and outcomes of referrals to pediatric inpatient hospice care and (2) a dataset on location of death for all pediatric patients who had any contact with the hospice system. Chi-square analyses were conducted to assess the associations between the PHF opening and referral outcomes and location of death. Results: Significant results were found with respect to both referral outcomes and location of death. Engagement in inpatient hospice care increased between 2- and 10-fold following the opening of the inpatient PHF. The percent of patients who died in an inpatient hospice unit also increased significantly with the opening of the pediatric facility. Discussion: Results of this study show that providers are more likely to refer, and families are more likely to use inpatient hospice services when pediatric facilities are available. These results are important for establishing an evidence base in support for increasing access to PHFs.

Microstructural Parameters for Modelling of Superconducting Foams.

Superconducting YBa2Cu3Oy (YBCO) foams were prepared using commercial open-cell, polyurethane foams as starting material to form ceramic Y2BaCuO5 foams which are then converted into superconducting YBCO by using the infiltration growth process. For modelling the superconducting and mechanical properties of the foam samples, a Kelvin-type cell may be employed as a first approach as reported in the literature for pure polyurethane foams. The results of a first modelling attempt in this direction are presented concerning an estimation of the possible trapped fields (TFs) and are compared to experimental results at 77 K. This simple modelling revealed already useful information concerning the best suited foam structure to realize large TF values, but it also became obvious that for various other parameters like magnetostriction, mechanical strength, percolative current flow and the details of the TF distribution, a refined model of a superconducting foam sample incorporating the real sample structure must be considered. Thus, a proper description of the specific microstructure of the superconducting YBCO foams is required. To obtain a set of reliable data, YBCO foam samples were investigated using optical microscopy, scanning electron microscopy and electron backscatter diffraction (EBSD). A variety of parameters including the size and shape of the cells and windows, the length and shape of the foam struts or ligaments and the respective intersection angles were determined to better describe the real foam structure. The investigation of the foam microstructures revealed not only the differences to the original polymer foams used as base material, but also provided further insights to the infiltration growth process via the large amount of internal surface in a foam sample.

Improving suspicious breast lesion characterization using semi-automatic lesion fractional volume washout kinetic analysis.

PURPOSE: Although breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) demonstrates high sensitivity for malignant tumor detection, a major limitation is the relative low specificity, resulting in many false-positive diagnoses of suspicious lesions (BI-RADS assessment of 4 or 5) in clinical practice and consequently producing a relatively low positive predictive value (PPV) for biopsies. The most enhanced areas in the malignant tumors show a typical washout (WO) kinetic feature for the postcontrast signal intensity time courses and also correlate with microvessel density. Benign proliferative breast diseases can also produce the WO curve, yielding an equivocal kinetic behavior for the benign lesions and rendering their diagnoses as suspicious lesions in clinical practice. Considering that tumor angiogenesis is essential to an aggressive cancer tumor growth, the authors hypothesize that the WO volume fraction, i.e., the total volume of the WO voxels that demonstrate the WO curve within the tumor, is relatively large for malignant tumors in comparison to that for benign lesions. In this study, the authors present a lesion fractional volume WO kinetic analysis for improving the characterization of suspicious breast lesions. METHODS: A method to automatically detect the boundary of a manually selected contrast-enhanced lesion was introduced and tested, utilizing the signal intensity difference between the contrast-enhanced lesion and its surrounding tissues. The kinetic features of the postcontrast signal intensity time courses were quantitatively analyzed voxel-by-voxel with emphasis on the examination of the WO behavior. The WO volume fraction relative to the whole lesion volume was introduced and tested as a biomarker for improving the characterization of suspicious breast lesions. The sample for this test consisted of 28 suspicious lesions with correlative histopathology reports available. The lesions included 10 malignant tumors and 18 benign lesions, yielding a 35.7% PPV of the biopsies. RESULTS: The semi-automatic method produced an objective volume of interest for each lesion with voxelwise-quantified kinetic features. With an optimal choice of kinetic analysis, the mean and standard deviation of the WO volume fraction were 59.1 ± 13.1 (%) with the range from 41.0% to 80.7% for the malignant tumors and 31.4 ± 20.5 (%) with the range between 3.3% and 71.6% for the benign lesions, respectively. The WO volume fraction was significantly larger (p < 0.0004) for the malignant tumors than for the benign lesions. While maintaining the same sensitivity for malignant tumors, using the WO volume fraction as an additional biomarker would characterize 14 out of the 18 benign lesions as benign, potentially resulting in an 100% improvement rate in the PPV of the biopsies (from 35.7% to 71.4%) and consequently a 77.8% reduction rate in potentially unnecessary biopsies (from 18 to 4). CONCLUSIONS: The significantly larger WO volume fraction for the malignant tumors was probably related to the increased vascularity associated with tumor angiogenesis. The results suggest that the WO volume fraction biomarker has potential to improve the computer-based assessment of breast MRI by greatly increasing the PPV of breast biopsies and potentially significantly reducing the number of unnecessary biopsies without compromising sensitivity.

Characterization of High-Temperature Superconductor Bulks for Electrical Machine Application.

High-temperature superconducting (HTS) bulks can be used in electrical applications. Experimental characterization of large-size HTS bulks is a tricky issue. The relevant parameters for their application were directly measured in this study. This paper has three main aims. Firstly, features of YBaCuO bulks are presented. Secondly, an electrical motor application is developed using magnetic field shielding and trapping. Thirdly, the HTS bulks are characterized. Several classical methods were used, which are mainly magnetic methods only available for small samples. The complete penetration magnetic field and the critical current density were found to be the main parameters relevant for applications. An innovative entire HTS bulk characterization method is presented. This characterization method is useful for end users and engineers to better implement HTS bulks.

Review on the Use of Superconducting Bulks for Magnetic Screening in Electrical Machines for Aircraft Applications.

High-Temperature Superconductors (HTS) considerably accelerate the development of superconducting machines for electrical engineering applications such as fully electrical aircraft. This present contribution is an overview of different superconducting materials that can be used as magnetic screens for the inductor of high specific power electrical machines. The impact of the material properties, such as the critical temperature (Tc) and the critical current density (Jc), on the machine performances is evaluated. In addition, the relevance to flux modulation machines of different HTS bulk synthesis methods are addressed.

Fluorescent palladium(II) and platinum(II) NHC/1,2,3-triazole complexes: antiproliferative activity and selectivity against cancer cells.

Fluorescent Pd(ii) and Pt(ii) complexes bearing 4-methylene-7-methoxycoumarin (MMC) and 2,6-diispropylphenyl (Dipp) substituted NHC/1,2,3-triazole hybrid ligands are described. Depending on the reaction conditions two different ligand coordination modes are observed, i.e., bidentate solely coordinating via NHCs or tetradentate coordinating via NHCs and 1,2,3-triazoles. All Dipp substituted complexes show antiproliferative activity against cervix (HeLa) and breast (MCF-7) human carcinoma cells. The activity significantly depends on the coordination mode, with the tetradentate motif being notably more effective (HeLa: IC50 = 3.9 µM to 4.7 µM; MCF-7: IC50 = 2.07 µM to 2.35 µM). Amongst the MMC series, only the Pd(ii) complex featuring the bidentate coordination mode is active against HeLa (IC50 = 6.1 µM). In contrast to its structurally related Dipp derivative (SI = 0.6), it shows a high selectivity for HeLa (SI > 16) compared to healthy skin cells (HaCaT). According to fluorescence microscopy, this compound is presumably located in late endosomes or lysosomes.

Noninvasive detection and localization of vulnerable plaque and arterial thrombosis with computed tomography angiography/positron emission tomography.

BACKGROUND: It has been shown that plaque uptake of fluorodeoxyglucose is proportional to macrophage density. We tested the hypothesis that arterial thrombosis occurs in areas with high fluorodeoxyglucose uptake and that computed tomography angiography (CTA) can detect thrombi in vessels. METHODS AND RESULTS: Twenty New Zealand White rabbits were studied before and after atherosclerosis induction through de-endothelialization and a high-cholesterol diet; 14 were then thrombus triggered. CTA/positron emission tomography scans were performed before cholesterol diet, at the middle diet feeding, at the end of diet feeding, and after triggering. Serum inflammatory markers were measured. Maximal standardized uptake value was measured over the thoracic and upper and lower abdominal aortas and correlated with thrombosis and macrophage density on sections from the same sites. Aortic diameters averaged 2.84+/-1.16 mm. The sensitivity, specificity, and accuracy of CTA for detecting thrombi were 92%, 89%, and 90%, respectively. Plasminogen activator inhibitor-1 and C-reactive protein levels increased with atherosclerosis and thrombosis triggering. Maximal standardized uptake value at baseline was 0.62+/-0.13, 0.96+/-0.33 at the middle of feeding, and 1.06+/-0.38 at the end of feeding. Segments that developed thrombosis had the highest maximal standardized uptake value of 1.32+/-0.69 (113% increase; P=0.002) and had a 129% increase in macrophage density compared with segments without thrombi (P=0.01). CONCLUSIONS: Fluorodeoxyglucose uptake was proportional to the duration of cholesterol feeding and peaked with plaque disruption and thrombosis. CTA was highly accurate in detecting thrombi. Our findings in this animal model of atherosclerotic plaques with high macrophage density showed that CTA/positron emission tomography can be used to identify and localize inflamed plaques and thrombosis. With the currently available technology and nuclear tracers, however, many challenges remain before clinical applications are possible.

A network of chaperones prevents and detects failures in membrane protein lipid bilayer integration.

A fundamental step in membrane protein biogenesis is their integration into the lipid bilayer with a defined orientation of each transmembrane segment. Despite this, it remains unclear how cells detect and handle failures in this process. Here we show that single point mutations in the membrane protein connexin 32 (Cx32), which cause Charcot-Marie-Tooth disease, can cause failures in membrane integration. This leads to Cx32 transport defects and rapid degradation. Our data show that multiple chaperones detect and remedy this aberrant behavior: the ER-membrane complex (EMC) aids in membrane integration of low-hydrophobicity transmembrane segments. If they fail to integrate, these are recognized by the ER-lumenal chaperone BiP. Ultimately, the E3 ligase gp78 ubiquitinates Cx32 proteins, targeting them for degradation. Thus, cells use a coordinated system of chaperones for the complex task of membrane protein biogenesis, which can be compromised by single point mutations, causing human disease.

Publisher Correction: A network of chaperones prevents and detects failures in membrane protein lipid bilayer integration.

The original version of this Article contained errors in Fig. 1 and Supplementary Fig. 3. In Fig. 1, the labels indicating the Cx32wt constructs in panels d and e were incorrectly shifted with respect to the relevant western blot lanes. In Supplementary Fig. 3, numbers of unique peptides and % sequence coverage were incorrectly reported as being for wt and L90H separately, and should refer to wt and L90H combined. These errors have been corrected in the PDF and HTML versions of the Article.

Automated cardiac motion compensation in PET/CT for accurate reconstruction of PET myocardial perfusion images.

Error-free reconstruction of PET data with a registered CT attenuation map is essential for accurate quantification and interpretation of cardiac perfusion. Misalignment of the CT and PET data can produce an erroneous attenuation map that projects lung attenuation parameters onto the heart wall, thereby underestimating the attenuation and creating artifactual areas of hypoperfusion that can be misinterpreted as myocardial ischemia or infarction. The major causes of misregistration between CT and PET images are the respiratory motion, cardiac motion and gross physical motion of the patient. The misalignment artifact problem is overcome with automated cardiac registration software that minimizes the alignment error between the two modalities. Results show that the automated registration process works equally well for any respiratory phase in which the CT scan is acquired. Further evaluation of this procedure on 50 patients demonstrates that the automated registration software consistently aligns the two modalities, eliminating artifactual hypoperfusion in reconstructed PET images due to PET/CT misregistration. With this registration software, only one CT scan is required for PET/CT imaging, which reduces the radiation dose required for CT-based attenuation correction and improves the clinical workflow for PET/CT.

Breast MR imaging: applications and pitfalls.

CONTEXT: Contrast-enhanced magnetic resonance (MR) imaging provides better detail of the breast than either mammography or ultrasound imaging and can be a valuable adjunct to other imaging techniques, particularly for small lesions, in dense or augmented breasts and for treatment planning. OBJECTIVE: To illustrate some common technical problems encountered with MR imaging of the breast and present breast pathologies depicted with MR. RESULTS: Using a case-study approach, the authors discuss breast MR imaging difficulties related to hardware, software, technologist performance and patient cooperation. They also present examples of contralateral breast cancer, recurrent breast carcinoma and local staging of breast cancer with MR imaging. Summary MR imaging of the breast has important advantages over other techniques, despite occasional technical problems.