Stereochemistry of polypeptoid chain configurations.

Like polypeptides, peptoids, or N-substituted glycine oligomers, have intrinsic conformational preferences due to their amide backbones and close spacing of side chain substituents. However, the conformations that peptoids adopt are distinct from polypeptides due to several structural differences: the peptoid backbone is composed of tertiary amide bonds that have trans and cis conformers similar in energy, they lack a backbone hydrogen bond donor, and have an N-substituent. To better understand how these differences manifest in actual peptoid structures, we analyzed 46 high quality, experimentally determined peptoid structures reported in the literature to extract their backbone conformational preferences. One hundred thirty-two monomer dihedral angle pairs were compared to the calculated energy landscape for the peptoid Ramachandran plot, and were found to fall within the expected minima. Interestingly, only two regions of the backbone dihedral angles ϕ and ψ were found to be populated that are mirror images of each other. Furthermore, these two conformers are present in both cis and trans forms. Thus, there are four primary conformers that are sufficient to describe almost all known backbone conformations for peptoid oligomers, despite conformational constraints imposed by a variety of side chains, macrocyclization, or crystal packing forces. Because these conformers are predominant in peptoid structure, and are distinct from those found in protein secondary structures, we propose a simple naming system to aid in the description and classification of peptoid structure.

Exome sequencing reveals a novel COL2A1 mutation implicated in multiple epiphyseal dysplasia.

Mutations in the COMP, COL9A1, COL9A2, COL9A3, MATN3, and SLC26A2 genes cause approximately 70% of multiple epiphyseal dysplasia (MED) cases. The genetic changes involved in the etiology of the remaining cases are still unknown, suggesting that other genes contribute to MED development. Our goal was to identify a mutation causing an autosomal dominant form of MED in a large multigenerational family. Initially, we excluded all genes known to be associated with autosomal dominant MED by using microsatellite and SNP markers. Follow-up with whole-exome sequencing analysis revealed a mutation c.2032G>A (p.Gly678Arg) in the COL2A1 gene (NCBI Reference Sequence: NM_001844.4), which co-segregated with the disease phenotype in this family, manifested by severe hip dysplasia and osteoarthritis. One of the affected family members had a double-layered patella, which is frequently seen in patients with autosomal recessive MED caused by DTDST mutations and sporadically in the dominant form of MED caused by COL9A2 defect.

Aging is associated with impaired angiogenesis, but normal microvascular network structure, in the rat mesentery.

A big problem associated with aging is thought to be impaired microvascular growth or angiogenesis. However, to link the evidence for impaired angiogenesis to microvascular dysfunction in aged tissues, we must compare adult vs. aged microvascular networks in unstimulated scenarios. The objective of this study was to test the hypothesis that aged microvascular networks are characterized by both fewer vessels and the impaired ability to undergo angiogenesis. Mesentery tissues from adult (9-mo) and aged (24-mo) male Fischer 344 rats were harvested and immunolabeled for platelet/endothelial cell adhesion molecule (an endothelial cell marker) according to two scenarios: unstimulated and stimulated. For unstimulated groups, tissues harvested from adult and aged rats were compared. For stimulated groups, tissues were harvested 3 or 10 days after compound 48/80-induced mast cell degranulation stimulation. Unstimulated aged microvascular networks displayed larger mean vascular area per tissue area compared with the unstimulated adult networks. The lack of a decrease in vessel density was supported at the gene expression level with RNA-Seq analysis and with comparison of vessel densities in soleus muscle. Following stimulation, capillary sprouting and vessel density were impaired in aged networks at 3 and 10 days, respectively. Our results suggest that aging associated with impaired angiogenesis mechanisms might not influence normal microvascular function, since unstimulated aged microvascular networks can display a "normal adult-like" vessel density and architecture. NEW & NOTEWORTHY: Using a multidimensional approach, we present evidence supporting that aged microvascular networks display vessel density and patterning similar to adult networks despite also being characterized by a decreased capacity to undergo angiogenesis. Thus, vessel loss is not necessarily a characteristic of aging.

Incidental Thyroid Nodules on CT or MRI: Discordance Between What We Report and What Receives Workup.

OBJECTIVE: The objective of this study was to determine the proportion of incidental thyroid nodules (ITNs) reported on CT or MRI that receive additional workup and the factors that influence workup. A secondary aim was to evaluate the effect of the American College of Radiology (ACR) white paper recommendations for reporting of ITNs. MATERIALS AND METHODS: We retrospectively reviewed patients with ITNs reported on CT or MRI studies over 12 months. We identified patients with ITNs that underwent workup and the factors associated with workup. The ACR white paper recommendations were retrospectively applied to estimate how their use would have changed the number of nodules reported in the impression section of radiology reports and the number of cancers diagnosed. The recommendations are based on suspicious imaging features, patient age, and nodule size. RESULTS: A total of 375 patients had ITNs reported. For 138 of these patients (37%), ITNs were reported by radiologists in the impression section of their reports; 26 patients (19%) received workup. Patients with ITNs reported in the impression section were 14 times more likely to undergo workup than were patients with ITNs reported only in the findings section of the radiology report. On multivariate analysis, the only factors associated with workup were younger patient age and larger nodule size (p ≤ 0.002). The ACR recommendations resulted in a 54% reduction in the number of ITNs reported in the impression section and one missed papillary cancer (TNM classification T1bN0M0). CONCLUSION: Only one in five patients with ITNs reported in the impression section of CT or MRI reports underwent additional workup, and this decision was influenced by younger patient age and larger nodule size. These factors are components of the ACR recommendations, which have the potential to reduce the number of reported ITNs and improve the standardization of radiology reporting.

Applying the Society of Radiologists in Ultrasound recommendations for fine-needle aspiration of thyroid nodules: effect on workup and malignancy detection.

OBJECTIVE: The Society of Radiologists in Ultrasound (SRU) recommendations on thyroid nodules are intended to "diagnose thyroid cancers that have reached clinical significance, while avoiding unnecessary tests and surgery in patients with benign nodules." The aim of our study was to determine the proportion of thyroid nodules undergoing ultrasound-guided fine-needle aspiration (FNA) that do not meet SRU recommendations. MATERIALS AND METHODS: This study is a retrospective study of 400 consecutive ultrasound-guided thyroid FNA encounters from July 2010 through June 2011. An encounter was defined as presentation to the department of radiology on a given date for FNA of one or more thyroid nodules. The criteria for performing biopsy of a nodule were determined by the referring clinicians. Nodules were categorized on the basis of sonographic findings as meeting SRU recommendations for biopsy, which we refer to as "SRU-positive," or not, which we refer to as "SRU-negative." Patients without a definitive pathology diagnosis of Bethesda class benign or malignant nodules were excluded. The characteristics of malignancies were compared for SRU-positive and SRU-negative encounters. RESULTS: The final study group consisted of 360 biopsy encounters for 350 patients and 29 malignancies (8%). Of the 360 biopsy encounters, 86 (24%) were SRU-negative encounters. Malignancy rates in SRU-positive and SRU-negative encounters were 9% (24/274) and 6% (5/86), respectively, and were not significantly different (p=0.5). Eighteen malignancies (75%) in the SRU-positive group were localized, whereas the others had nodal metastases (4/24) or distant metastases (2/24). SRU-positive encounters included medullary carcinoma, anaplastic carcinoma, and melanoma metastasis in addition to papillary carcinoma. All SRU-negative malignancies were localized papillary carcinomas. CONCLUSION: One in four thyroid biopsy encounters at our institution did not meet SRU recommendations for biopsy. The application of SRU recommendations reduces the number of benign nodules that undergo workup. Potentially missed malignancies in SRU-negative nodules are less aggressive by histologic type and stage compared with SRU-positive malignancies.

Kartograf: A Geometrically Accurate Atom Mapper for Hybrid-Topology Relative Free Energy Calculations.

Relative binding free energy (RBFE) calculations have emerged as a powerful tool that supports ligand optimization in drug discovery. Despite many successes, the use of RBFEs can often be limited by automation problems, in particular, the setup of such calculations. Atom mapping algorithms are an essential component in setting up automatic large-scale hybrid-topology RBFE calculation campaigns. Traditional algorithms typically employ a 2D subgraph isomorphism solver (SIS) in order to estimate the maximum common substructure. SIS-based approaches can be limited by time-intensive operations and issues with capturing geometry-linked chemical properties, potentially leading to suboptimal solutions. To overcome these limitations, we have developed Kartograf, a geometric-graph-based algorithm that uses primarily the 3D coordinates of atoms to find a mapping between two ligands. In free energy approaches, the ligand conformations are usually derived from docking or other previous modeling approaches, giving the coordinates a certain importance. By considering the spatial relationships between atoms related to the molecule coordinates, our algorithm bypasses the computationally complex subgraph matching of SIS-based approaches and reduces the problem to a much simpler bipartite graph matching problem. Moreover, Kartograf effectively circumvents typical mapping issues induced by molecule symmetry and stereoisomerism, making it a more robust approach for atom mapping from a geometric perspective. To validate our method, we calculated mappings with our novel approach using a diverse set of small molecules and used the mappings in relative hydration and binding free energy calculations. The comparison with two SIS-based algorithms showed that Kartograf offers a fast alternative approach. The code for Kartograf is freely available on GitHub (https://github.com/OpenFreeEnergy/kartograf). While developed for the OpenFE ecosystem, Kartograf can also be utilized as a standalone Python package.

Physician self-referral: frequency of negative findings at MR imaging of the knee as a marker of appropriate utilization.

PURPOSE: To determine whether ownership of magnetic resonance (MR) imaging equipment by ordering physicians affects the likelihood of positive findings at MR imaging of the knee and to evaluate rates of knee abnormalities seen at MR imaging as a metric for comparison of utilization. MATERIALS AND METHODS: The institutional review board approved this retrospective HIPAA-compliant study and waived the need for informed consent. A retrospective review was performed of consecutive diagnostic MR images of the knee interpreted by one radiology practice between January and April 2009 for patients who had been referred by two separate physician groups serving the same geographic community: one with financial interest (FI) in the MR imaging equipment used and one with no FI (NFI) in the MR imaging equipment used. The percentage of examinations with negative results was tabulated for both groups, and the relative frequency of each abnormality subtype was calculated among the studies with positive findings in each group. To examine frequency differences among groups, χ(2) tests were used, and to examine mean differences among groups, t tests were used. RESULTS: Of 700 examinations, 205 had negative results (117 of 350 in the FI group and 88 of 350 in the NFI group, P = .016). Among the examinations with positive results, the mean total number of positive abnormality subtypes per image did not significantly differ between groups: 1.52 for the FI group and 1.53 for the NFI group (P = .96). CONCLUSION: MR images of the knee among patients referred by the FI group were significantly more likely to be negative than those among patients referred by the NFI group. Frequency of abnormality subtype and distribution among examinations with positive results suggests a highly similar distribution and severity of abnormalities between the two patient groups.

Journal Club: Shoulder MRI utilization: relationship of physician MRI equipment ownership to negative study frequency.

OBJECTIVE: The purpose of this article is to determine whether ownership of MRI equipment by ordering physicians influences the frequency of negative shoulder MRI scans. MATERIALS AND METHODS: A retrospective review was performed of 1140 consecutive shoulder MRI scans ordered by two separate referring physician groups serving the same geographic community. The first group (financially incentivized) owned the scanners used and received technical fees for their use. The second group (non-financially incentivized) did not own the scanners used and had no direct financial interest. All examinations were performed with identical protocols and were interpreted by a single radiologist group without financial interest in the imaging equipment used. The frequency of negative examinations and the number of abnormalities in each positive study was tabulated for each group. RESULTS: A total of 1140 shoulder MRI scans met inclusion criteria; 255 were negative (142 for the financially incentivized group and 113 for the non-financially incentivized group). There were 25.6% more negative scans in the financially incentivized group (p=0.047). There was no statistically significant difference in the average number of lesions per positive scan (1.67 for the financially incentivized group and 1.71 for the non-financially incentivized group; p=0.34). No statistically significant difference was found in the frequency of 19 of 20 examined lesions. CONCLUSION: Shoulder MRI examinations referred by physicians with a financial interest in the imaging equipment used were significantly more likely to be negative. Positive examinations exhibited no statistically significant difference in the number of lesions per scan or in the frequency of 19 of 20 lesion subtypes. This finding suggests a highly similar distribution and severity of disease among the two patient groups.

Physician self-referral of lumbar spine MRI with comparative analysis of negative study rates as a marker of utilization appropriateness.

OBJECTIVE: Financial interest in imaging equipment may affect the imaging referral patterns of ordering physicians. The purpose of this article is to determine whether ownership of MRI equipment by ordering physicians predicts the likelihood and prevalence of positive findings on lumbar spine MRI as a metric for comparison of utilization. MATERIALS AND METHODS: A retrospective review was performed of 500 consecutive diagnostic lumbar spine MRI examinations in one radiology practice ordered by two separate referring physician groups serving the same geographic community: one with financial interest in the MRI equipment used (financial-interest group) and one without financial interest in the MRI equipment used (no-financial-interest group). Negative examinations and total number of lesions per positive study were recorded for each group. RESULTS: Five hundred scans met inclusion criteria during the study period (250 in the financial-interest group and 250 in the no-financial-interest group). The negative scan frequency was 86% higher in the financial-interest group (p < 0.0001). Among positive scans, there was no significant difference in the average total number of positive lesions per scan (3.93 for the financial-interest group and 4.31 for the no-financial-interest group; p = 0.132). The average age of patients imaged by the financial-interest group was 49.8 years, versus 56.9 years for the no-financial-interest group (p < 0.0001). CONCLUSION: Lumbar spine MRI examinations referred by the financial-interest group were significantly more likely to be negative than those referred by the no-financial-interest group. Lesion frequency among positive scans suggests similar severity of disease between the two patient populations. Patients imaged by the financial-interest group were significantly younger than those imaged by the no-financial-interest group.

Variation in tube voltage for adult neck MDCT: effect on radiation dose and image quality.

OBJECTIVE: The purpose of this study was to assess the effect of peak kilovoltage on radiation dose and image quality in adult neck MDCT. MATERIALS AND METHODS: An anthropomorphic phantom with metal oxide semiconductor field effect transistor detectors was imaged with a 64-MDCT scanner. The reference CT protocol called for 120 kVp, and images obtained with that protocol were compared with CT images obtained with protocols entailing 80, 100, and 140 kVp. All imaging was performed with automatic tube current modulation. Organ dose and effective dose were determined for each protocol and compared with those obtained with the 120-kVp protocol. Image noise was evaluated objectively and subjectively for each protocol. RESULTS: The highest organ doses for all protocols were to the thyroid, ocular lens, skin, and mandible. The greatest reductions in organ dose were for the bone marrow of the cervical spine and mandible: 43% and 35% with the 100-kVp protocol and 63% and 53% with the 80-kVp protocol. Effective dose decreased as much as 9% with the 100-kVp protocol and 12% with the 80-kVp protocol. Use of the 140-kVp protocol was associated with an increase in organ dose as high as 64% for bone marrow in the cervical spine and a 19% increase in effective dose. Image noise increased with lower peak kilovoltage. The measured noise difference was greatest at 80 kVp, absolute increases were less than 2.5 HU. There was no difference in subjective image quality among protocols. CONCLUSION: Reducing the voltage from 120 to 80 kVp for neck CT can result in greater than 50% reduction in the absorbed organ dose to the bone marrow of the cervical spine and mandible without impairment in subjective image quality.

Organ-based dose current modulation and thyroid shields: techniques of radiation dose reduction for neck CT.

OBJECTIVE: The purpose of this study was to assess the difference in absorbed organ dose and image quality for MDCT neck protocols using automatic tube current modulation alone compared with organ-based dose modulation and in-plane thyroid bismuth shielding. MATERIALS AND METHODS: An anthropomorphic female phantom with metal oxide semiconductor field effect transistor (MOSFET) detectors was scanned on a 64-MDCT scanner. The protocols included a reference neck CT protocol using automatic tube current modulation and three modified protocols: organ-based dose modulation, automatic tube current modulation with thyroid shield, and organ-based dose modulation with thyroid shield. Image noise was evaluated quantitatively with the SD of the attenuation value, and subjectively by two neuroradiologists. RESULTS: Organ-based dose modulation, automatic tube current modulation with thyroid shield, and organ-based dose modulation with thyroid shield protocols reduced the thyroid dose by 28%, 33%, and 45%, respectively, compared with the use of automatic tube current modulation alone (p ≤ 0.005). Organ-based dose modulation also reduced the radiation dose to the ocular lens (33-47%) compared with the use of automatic tube current modulation (p ≤ 0.04). There was no significant difference in measured noise and subjective image quality between the protocols. CONCLUSION: Both organ-based dose modulation and thyroid shields significantly reduce the thyroid organ dose without degradation of subjective image quality compared with automatic tube current modulation. Organ-based dose modulation has the additional benefit of dose reduction to the ocular lens.

Evaluating the Conformations and Dynamics of Peptoid Macrocycles.

Peptoid macrocycles are versatile and chemically diverse peptidomimetic oligomers. However, the conformations and dynamics of these macrocycles have not been evaluated comprehensively and require extensive further investigation. Recent studies indicate that two degrees of freedom, and four distinct conformations, adequately describe the behavior of each monomer backbone unit in most peptoid oligomers. On the basis of this insight, we conducted molecular dynamics simulations of model macrocycles using an exhaustive set of idealized possible starting conformations. Simulations of various sizes of peptoid macrocycles yielded a limited set of populated conformations. In addition to reproducing all relevant experimentally determined conformations, the simulations accurately predicted a cyclo-octamer conformation for which we now present the first experimental observation. Sets of three adjacent dihedral angles (ϕi, ψi, ωi+1) exhibited correlated crankshaft motions over the course of simulation for peptoid macrocycles of six residues and larger. These correlated motions may occur in the form of an inversion of one amide bond and the concerted rotation of the preceding ϕ and ψ angles to their mirror-image conformation, a variation on "crankshaft flip" motions studied in polymers and peptides. The energy landscape of these peptoid macrocycles can be described as a network of conformations interconnected by transformations of individual crankshaft flips. For macrocycles of up to eight residues, our mapping of the landscape is essentially complete.

Correlation of cross-sectional diameter with image quality and radiation exposure in MDCT examinations of the neck.

OBJECTIVE: The purpose of this study was to identify an optimal cross-sectional neck diameter that correlates with image quality and radiation exposure in MDCT examinations of the neck performed with automatic tube current modulation. MATERIALS AND METHODS: Ninety-six adults underwent 64-MDCT of the neck with automatic tube current modulation at the same noise setting. On frontal and lateral scout images, maximal body diameters were measured in the transverse and anteroposterior planes at two levels: just below the mandible (upper neck) and at the lung apex (lower neck). Neck diameters were correlated with image quality on a subjective 4-point scale and with radiation exposure (volume CT dose index). RESULTS: As continuous variables, both anteroposterior and transverse diameters in the lower neck were associated with image quality (p ≤ 0.0012). Diameters in the upper neck were not associated with image quality. When diameters in the lower neck were categorized into small, medium, and large, image quality grades were higher for smaller patients (p < 0.001). Images of 81% of small patients (lower neck transverse diameter < 40 cm) had a high image quality grade, compared with images of 7-20% of large patients (diameter > 48 cm). Transverse diameter in the lower neck correlated best with radiation dose measured as volume CT dose index (r = 0.78). When transverse diameter in the lower neck was used to categorize patients' size, the mean volume CT dose index for small patients was 34.1 mSv and that for large patients was 63.5 mSv. CONCLUSION: Lower neck transverse diameter on the CT scout image best correlates with image quality and radiation exposure for neck MDCT examinations performed with automatic tube current modulation. Images of patients with a lower neck transverse diameter less than 40 cm are of higher quality than those of larger patients. Individualized dose reduction techniques therefore may be appropriate for smaller patients.

Multiplanar CT and MRI of collections in the retropharyngeal space: is it an abscess?

OBJECTIVE: The purpose of this article is to describe a practical imaging approach to evaluating collections in the retropharyngeal space. CONCLUSION: The differential diagnoses for fluid in the retropharyngeal space include both noninfectious and infectious processes. The multiplanar capabilities of CT and MRI are ideal for characterizing and delineating collections. In this pictorial essay, we describe the anatomy of the retropharyngeal space and offer a four-step approach to evaluating retropharyngeal collections on multiplanar imaging.

Radiation dose exposure for lumbar spine epidural steroid injections: a comparison of conventional fluoroscopy data and CT fluoroscopy techniques.

OBJECTIVE: The purpose of this article is to compare the radiation dose of conventional fluoroscopy-guided lumbar epidural steroid injections (ESIs) and CT fluoroscopy (CTF)-guided lumbar ESI using both clinical data and anthropomorphic phantoms. MATERIALS AND METHODS: We performed a retrospective review of dose parameters for 14 conventional fluoroscopy ESI procedures performed by one proceduralist and 42 CTF-guided ESIs performed by three proceduralists (14 each). By use of imaging techniques similar to those for our clinical cohorts, a commercially available anthropomorphic male phantom with metal oxide semiconductor field effect transistor detectors was scanned to obtain absorbed organ doses for conventional fluoroscopy-guided and CTF-guided ESIs. Effective dose (ED) was calculated from measured organ doses. RESULTS: The mean conventional fluoroscopy time for ESI was 37 seconds, and the mean procedural CTF time was 4.7 seconds. Calculated ED for conventional fluoroscopy was 0.85 mSv compared with 0.45 mSv for CTF. The greatest contribution to the radiation dose from CTF-guided ESI came from the planning lumbar spine CT scan, which had an ED of 2.90 mSv when z-axis ranged from L2 to S1. This resulted in a total ED for CTF-guided ESI (lumbar spine CT scan plus CTF) of 3.35 mSv. CONCLUSION: The ED for the CTF-guided ESI was almost half that of conventional fluoroscopy because of the shorter fluoroscopy time. However, the overall radiation dose for CTF-guided ESIs can be up to four times higher when a full diagnostic lumbar CT scan is performed as part of the procedure. Radiation dose reduction for CTF-guided ESI is best achieved by minimizing the dose from the preliminary planning lumbar spine CT scan.

Fe(x)Pb(4-x)Sb4Se10: a new class of ferromagnetic semiconductors with quasi 1D {Fe2Se10} ladders.

A new family of quasi-one-dimensional ferromagnetic selenides with general formula Fe(x)Pb(4-x)Sb(4)Se(10) (0 < or = x < or = 2) was generated by isoelectronic substitution in octahedral positions of Pb atoms by Fe within the structure of Pb(4)Sb(4)Se(10). Two members of this family with x = 0.75 and x = 1 were synthesized as a single phase through direct combination of the elements at 823 K. Single crystal X-ray diffraction revealed that Fe(0.75)Pb(3.25)Sb(4)Se(10) crystallizes with the orthorhombic space group Pnma, whereas Fe(0.96)Pb(3.04)Sb(4)Se(10) adopts the lower symmetry monoclinic subgroup P2(1)/m (#11). Both compounds are isomorphous with Pb(4)Sb(4)Se(10), and their crystal structures consist of corrugated layers of edge-sharing bicapped trigonal prisms and octahedra around Pb atoms. Adjacent layers are interconnected by NaCl-type {SbSe} ribbons. The voids left by this arrangement are filled by the novel one-dimensional {Fe(2)Se(10)} double chains (ladder) of edge-sharing octahedra running along [010]. Temperature dependent magnetic susceptibility as well as field dependent magnetization isotherms showed that both Fe(0.75)Pb(3.25)Sb(4)Se(10) and FePb(3)Sb(4)Se(10) are ferromagnetic below 300 K and exhibit superparamagnetism at higher temperatures. A dramatic reduction in the magnetic moment per Fe(2+), approximately 0.40 micro(B), was observed in Fe(0.75)Pb(3.25)Sb(4)Se(10) and FePb(3)Sb(4)Se(10) suggesting that the Fe(x)Pb(4-x)Sb(4)Se(10) (0 < or = x < or = 2) phases are not ordinary ferromagnets where all the magnetic spins are parallel at low temperatures. Analysis of the magnetic coupling of spins located on adjacent Fe atoms (within a localized Fe(2+) moment picture) using Goodenough-Kanamori rules suggested that the magnetism within the ladder and ladder-single chain systems in Fe(x)Pb(4-x)Sb(4)Se(10) phases is controlled by competing interactions.

Multiplanar sinus CT: a systematic approach to imaging before functional endoscopic sinus surgery.

OBJECTIVE: The purpose of this essay is to present a systematic approach to the use of coronal, axial, and sagittal images for CT evaluation of the sinuses before functional endoscopic sinus surgery (FESS). CONCLUSION: We present a systematic approach to the use of coronal, axial, and sagittal images in CT evaluation before FESS. Each imaging plane is valuable for displaying anatomic variants, which can predispose a patient to recurrent disease and affect the surgical approach, and critical variants, which can make surgery hazardous.

CT mucosal window settings: a novel approach to evaluating early T-stage head and neck carcinoma.

OBJECTIVE: The purpose of this study is to evaluate the CT densities of small head and neck mucosal cancers as a means of deriving a CT mucosal window display of narrower window width and higher window level to better detect and delineate head and neck carcinomas. MATERIALS AND METHODS: We retrospectively studied 19 subjects with T1-2 head and neck carcinomas. The density of tumor and adjacent normal mucosa on CT were measured. CT scans for the 19 patients with tumors and 35 subjects without mucosal tumors were anonymized and interpreted by two readers using standard soft-tissue windows and were reviewed again 1 week later with the addition of mucosal windows. RESULTS: The mean (± SD) attenuation of 17 visible tumors was 85.5 ± 18.3 Hounsfield units (HU) and that of the surrounding normal mucosa was 55.3 ± 15.2 HU (p < 0.0001). From our data, we derived guideline mucosal window settings-a window width of 120 HU and a window level of 60 HU. On blinded review, reader A detected 12 tumors with the addition of mucosal windows (sensitivity, 63%; specificity, 82%) and nine tumors on soft-tissue windows alone (sensitivity, 47%; specificity, 94%). Reader B detected nine tumors with use of mucosal windows (sensitivity, 47%; specificity, 71%) and eight tumors on soft-tissue windows alone (sensitivity, 42%; specificity, 74%). CONCLUSION: Early T-stage tumors have higher CT density than normal mucosa. Their conspicuity can be amplified using display windows with narrower window width and higher window level. The potential clinical applications are for the improved detection of unknown primary tumors and delineation of a known mucosal tumor.

Acute stroke imaging research roadmap.

The recent "Advanced Neuroimaging for Acute Stroke Treatment" meeting on September 7 and 8, 2007 in Washington DC, brought together stroke neurologists, neuroradiologists, emergency physicians, neuroimaging research scientists, members of the National Institute of Neurological Disorders and Stroke (NINDS), the National Institute of Biomedical Imaging and Bioengineering (NIBIB), industry representatives, and members of the US Food and Drug Administration (FDA) to discuss the role of advanced neuroimaging in acute stroke treatment. The goals of the meeting were to assess state-of-the-art practice in terms of acute stroke imaging research and to propose specific recommendations regarding: (1) the standardization of perfusion and penumbral imaging techniques, (2) the validation of the accuracy and clinical utility of imaging markers of the ischemic penumbra, (3) the validation of imaging biomarkers relevant to clinical outcomes, and (4) the creation of a central repository to achieve these goals. The present article summarizes these recommendations and examines practical steps to achieve them.

Multifocal anaplastic astrocytoma in a patient with hereditary colorectal cancer, transcobalamin II deficiency, agenesis of the corpus callosum, mental retardation, and inherited PMS2 mutation.

We describe the case of a patient with transcobalamin II deficiency, hypogammaglobulinemia, absent corpus callosum, and mental retardation who presented at an early age with colorectal cancer and multifocal anaplastic astrocytoma. He was found to have a possible germline mutation of the PMS2 gene, as evidenced by absent protein expression in both normal and tumor tissues. His parents were found to be carriers of a nonsense mutation of the PMS2 gene.