Integrative diagnostics: the time is now-a report from the International Society for Strategic Studies in Radiology.

Enormous recent progress in diagnostic testing can enable more accurate diagnosis and improved clinical outcomes. Yet these tests are increasingly challenging and frustrating; the volume and diversity of results may overwhelm the diagnostic acumen of even the most dedicated and experienced clinician. Because they are gathered and processed within the "silo" of each diagnostic discipline, diagnostic data are fragmented, and the electronic health record does little to synthesize new and existing data into usable information. Therefore, despite great promise, diagnoses may still be incorrect, delayed, or never made. Integrative diagnostics represents a vision for the future, wherein diagnostic data, together with clinical data from the electronic health record, are aggregated and contextualized by informatics tools to direct clinical action. Integrative diagnostics has the potential to identify correct therapies more quickly, modify treatment when appropriate, and terminate treatment when not effective, ultimately decreasing morbidity, improving outcomes, and avoiding unnecessary costs. Radiology, laboratory medicine, and pathology already play major roles in medical diagnostics. Our specialties can increase the value of our examinations by taking a holistic approach to their selection, interpretation, and application to the patient's care pathway. We have the means and rationale to incorporate integrative diagnostics into our specialties and guide its implementation in clinical practice.

Integrative Diagnostics: The Time Is Now-A Report From the International Society for Strategic Studies in Radiology.

Enormous recent progress in diagnostic testing can enable more accurate diagnosis and improved clinical outcomes. Yet these tests are increasingly challenging and frustrating; the volume and diversity of results may overwhelm the diagnostic acumen of even the most dedicated and experienced clinician. Because they are gathered and processed within the "silo" of each diagnostic discipline, diagnostic data are fragmented, and the electronic health record does little to synthesize new and existing data into usable information. Therefore, despite great promise, diagnoses may still be incorrect, delayed, or never made. Integrative diagnostics represents a vision for the future, wherein diagnostic data, together with clinical data from the electronic health record, are aggregated and contextualized by informatics tools to direct clinical action. Integrative diagnostics has the potential to identify correct therapies more quickly, modify treatment when appropriate, and terminate treatment when not effective, ultimately decreasing morbidity, improving outcomes, and avoiding unnecessary costs. Radiology, laboratory medicine, and pathology already play major roles in medical diagnostics. Our specialties can increase the value of our examinations by taking a holistic approach to their selection, interpretation, and application to the patient's care pathway. We have the means and rationale to incorporate integrative diagnostics into our specialties and guide its implementation in clinical practice.

Correlating the Radiological Assessment of Patient Motion with the Incidence of Repeat Sequences Documented by Log Files.

OBJECTIVE: To correlate a radiological assessment of MR motion artifacts with the incidence of repeated sequences and delays derived from modality log files (MLFs) and investigate the suitability of log files for quantifying the operational impact of patient motion. MATERIALS AND METHODS: An experienced, blinded neuroradiologist retrospectively evaluated one full calendar month of sequentially obtained clinical MR exams of the head and/or brain for the presence of motion artifacts using a previously defined clinical grading scale. MLF data were analyzed to extract the occurrence of repeated sequences during the examinations. Statistical analysis included the determination of 95% confidence intervals for repetition ratios, and Welch's t-test to exclude the hypothesis of equal means for different groups of sequences. RESULTS: A total of 213 examinations were evaluated, comprising 1681 MLF-documented sequences, from which 1580 were archived. Radiological motion assessment scores (0, none to 4, severe) were assigned to each archived sequence. Higher motion scores correlated with a higher MLF-derived repetition probability, reflected by the average motion scores assigned to sequences that would be repeated (group 1, mean=2.5), those that are a repeat (group 2, mean=1.9), and those that are not repeated (group 3, mean=1.1) within an exam. The hypothesis of equal means was rejected with P = 5.9 × 10-5 for groups 1 and 2, P = 9.39 × 10-16 for groups 1 and 3, and P = 1.55 × 10-12 for groups 2 and 3. The repetition probability and associated time loss could be quantified for individual sequence types. The total time loss due to repeat sequence acquisition derived from MLFs was greater than four hours. CONCLUSION: Log file data may help assess patterns of scanner and exam performance and may be useful in identifying pitfalls to diagnostic imaging in a clinical environment, particularly with respect to patient motion.

Elevated levels of Merkel cell polyoma virus in the anophthalmic conjunctiva.

The human ocular surface hosts a paucibacterial resident microbiome and virome. The factors contributing to homeostasis of this mucosal community are presently unknown. To determine the impact of ocular enucleation and prosthesis placement on the ocular surface microbiome, we sampled conjunctival swabs from 20 anophthalmic and 20 fellow-eye intact conjunctiva. DNA was extracted and subjected to quantitative 16S rDNA PCR, biome representational karyotyping (BRiSK), and quantitative PCR (qPCR) confirmation of specific organisms. 16S ribosomal qPCR revealed equivalent bacterial loads between conditions. Biome representational in silico karyotyping (BRiSK) demonstrated comparable bacterial fauna between anophthalmic and intact conjunctiva. Both torque teno virus and Merkel cell polyoma virus (MCPyV) were detected frequently in healthy and anophthalmic conjunctiva. By qPCR, MCPyV was detected in 19/20 anophthalmic samples compared with 5/20 fellow eyes. MCPyV copy number averaged 891 copies/ng in anophthalmic conjunctiva compared with 193 copies/ng in fellow eyes (p < 0.001). These results suggest that enucleation and prosthesis placement affect the ocular surface flora, particularly for the resident virome. As MCPyV has been shown to be the etiologic cause of Merkel cell carcinoma, understanding the mechanisms by which the ocular surface regulates this virus may have clinical importance.

Novel ultrasmall multifunctional nanodots for dual-modal MR/NIR-II imaging-guided photothermal therapy.

Encouraging progress in multifunctional nanotheranostic agents that combine photothermal therapy (PTT) and different imaging modalities has been made. However, rational designed and biocompatible multifunctional agents that suitfable for in vivo application is highly desired but still challenging. In this work, we rationally designed novel ultrasmall multifunctional nanodots (FS-GdNDs) by combining the bovine serum albumin (BSA)-based gadolinium oxide nanodots (GdNDs) obtained through a biomineralization process with a small-molecule NIR-II fluorophore (FS). The as-prepared FS-GdNDs with an ultrasmall hydrodynamic diameter of 9.3 nm exhibited prominent NIR-II fluorescence properties, high longitudinal relaxivity (10.11 mM-1 s-1), and outstanding photothermal conversion efficiency (43.99%) and photothermal stability. In vivo studies showed that the FS-GdNDs with enhanced multifunctional characteristics diaplayed satisfactory dual-modal MR/NIR-II imaging performance with a quite low dose. The imaging-guided PTT achieved successful ablation of tumors and effectively extended the survival of mice. Cytotoxicity studies and histological assay demonstrated excellent biocompatibility of the nanodots. Importantly, this novel FS-GdNDs can undergo efficient body clearance through both hepatobiliary and renal excretion pathways. The novel ultrasmall multifunctional FS-GdNDs with excellent features hold tremendous potential in biomedical and clinical applications.

Revisiting Current Golden Rules in Managing Acute Ischemic Stroke: Evaluation of New Strategies to Further Improve Treatment Selection and Outcome.

OBJECTIVE: Advanced stroke imaging has generated much excitement for the early diagnosis of acute ischemic stroke (AIS) and facilitation of intervention. However, its therapeutic impact has not matched its diagnostic utility; most notably, lacking significant contributions to recent major AIS clinical trials. It is time to reexamine the fundamental hypotheses from the enormous body of imaging research on which clinical practices are based and reassess the current standard clinical and imaging strategies, or golden rules, established over decades for AIS. In this article, we will investigate a possible new window of opportunity in managing AIS through a better understanding of the following: first, the potential limitations of the golden rules; second, the significance of imaging-based parenchymal hypoperfusion (i.e., lower-than-normal relative cerebral blood flow [rCBF] may not be indicative of ischemia); third, the other critical factors (e.g., rCBF, collateral circulation, variable therapeutic window, chronicity of occlusion) that reflect more individual ischemic injury for optimal treatment selection; and, fourth, the need for penumbra validation in successfully reperfused patients (not in untreated patients). CONCLUSION: Individual variations in the therapeutic window, ischemic injury (rCBF), and chronicity of vascular lesion development have not been comprehensively incorporated in the standard algorithms used to manage AIS. The current established imaging parameters have not been consistently validated with successfully reperfused patients and rCBF to quantitatively distinguish between oligemia and ischemia and between penumbra and infarct core within ischemic tissue. A novel paradigm incorporating rCBF values or indirectly incorporating relative rCBF values with higher statistically powered imaging studies to more reliably assess the severity of ischemic injury and differentiate reversibility from viability within the area of imaging-based parenchymal hypoperfusion may provide a more personalized approach to treatment, including no treatment of infarction core, to further enhance outcomes.

Towards use of MRI-guided ultrasound for treating cerebral vasospasm.

Cerebral vasospasm is a major cause of morbidity and mortality in patients with subarachnoid hemorrhage (SAH), causing delayed neurological deficits in as many as one third of cases. Existing therapy targets induction of cerebral vasodilation through use of various drugs and mechanical means, with a range of observed efficacy. Here, we perform a literature review supporting our hypothesis that transcranially delivered ultrasound may have the ability to induce therapeutic cerebral vasodilation and, thus, may one day be used therapeutically in the context of SAH. Prior studies demonstrate that ultrasound can induce vasodilation in both normal and vasoconstricted blood vessels in peripheral tissues, leading to reduced ischemia and cell damage. Among the proposed mechanisms is alteration of several nitric oxide (NO) pathways, where NO is a known vasodilator. While in vivo studies do not point to a specific physical mechanism, results of in vitro studies favor cavitation induction by ultrasound, where the associated shear stresses likely induce NO production. Two papers discussed the effects of ultrasound on the cerebral vasculature. One study applied clinical transcranial Doppler ultrasound to a rodent complete middle cerebral artery occlusion model and found reduced infarct size. A second involved the application of pulsed ultrasound in vitro to murine brain endothelial cells and showed production of a variety of vasodilatory chemicals, including by-products of arachidonic acid metabolism. In sum, nine reviewed studies demonstrated evidence of either cerebrovascular dilation or elaboration of vasodilatory compounds. Of particular interest, all of the reviewed studies used ultrasound capable of transcranial application: pulsed ultrasound, with carrier frequencies ranging between 0.5 and 2.0 MHz, and intensities not substantially above FDA-approved intensity values. We close by discussing potential specific treatment paradigms of SAH and other cerebral ischemic disorders based on MRI-guided transcranial ultrasound.

Brain imaging findings in elderly adults and years of life, healthy life, and able life over the ensuing 16 years: the Cardiovascular Health Study.

OBJECTIVES: To determine whether elderly people with different patterns of magnetic resonance imaging (MRI) findings have different long-term outcomes. DESIGN: Longitudinal cohort study. SETTING: Cardiovascular Health Study. PARTICIPANTS: Individuals aged 65 and older were recruited (N = 5,888); 3,660 of these underwent MRI, and 3,230 without a stroke before MRI were included in these analyses. MEASUREMENTS: Cluster analysis of brain MRI findings was previously used to define five clusters: normal, atrophy, simple infarct, leukoaraiosis, and complex infarct. Participants were subsequently classified as healthy if they rated their health as excellent, very good, or good and as able if they did not report any limitations in activities of daily living (ADLs). Mean years of life (YoL), years of healthy life (YHL), and years of able life (YAL) were calculated over 16 years after the MRI and compared between clusters using unadjusted and adjusted regression analyses. RESULTS: Mean age of participants was 75.0. With 16 years of follow-up, mean YoL was 11.3; YHL, 8.0; and YAL, 8.4. Outcomes differed significantly between clusters. With or without adjustments, outcomes were all significantly better in the normal than complex infarct cluster. The three remaining clusters had intermediate results, significantly different from the normal and complex infarct clusters but not usually from one another. Over 16 years of follow-up, participants in the complex infarct cluster (n = 368) spent the largest percentage of their 8.4 years alive being sick (38%) and not able (38%). CONCLUSION: Findings on MRI scans in elderly adults are associated not only with long-term survival, but also with long-term self-rated health and limitation in ADLs. The combination of infarcts and leukoaraiosis carried the worst prognosis, presumably reflecting small vessel disease.

Validation of optimal DCE-MRI perfusion threshold to classify at-risk tumor imaging voxels in heterogeneous cervical cancer for outcome prediction.

PURPOSE: To classify tumor imaging voxels at-risk for treatment failure within the heterogeneous cervical cancer using DCE MRI and determine optimal voxel's DCE threshold values at different treatment time points for early prediction of treatment failure. MATERIAL AND METHOD: DCE-MRI from 102 patients with stage IB2-IVB cervical cancer was obtained at 3 different treatment time points: before (MRI 1) and during treatment (MRI 2 at 2-2.5 weeks and MRI 3 at 4-5 weeks). For each tumor voxel, the plateau signal intensity (SI) was derived from its time-SI curve from the DCE MRI. The optimal SI thresholds to classify the at-risk tumor voxels was determined by the maximal area under the curve using ROC analysis when varies SI value from 1.0 to 3.0 and correlates with treatment outcome. RESULTS: The optimal SI thresholds for MRI 1, 2 and 3 were 2.2, 2.2 and 2.1 for significant differentiation between local recurrence/control, respectively, and 1.8, 2.1 and 2.2 for death/survival, respectively. CONCLUSION: Optimal SI thresholds are clinically validated to quantify at-risk tumor voxels which vary with time. A single universal threshold (SI=1.9) was identified for all 3 treatment time points and remained significant for the early prediction of treatment failure.

A guide to the external review of an academic radiology department.

External reviews are used to evaluate a department on a routine basis or prior to reappointment or recruitment of a department chair. The Society of Chairs of Academic Radiology Departments (SCARD) developed a template that outlines important components of an external review report and a table that outlines the objective information that can be requested from the institution/department prior to the reviewer's site visit. The template is meant to facilitate a high-quality review and serve as a guide to a chair who is preparing for his/her first review, chairs who serve as external consultants, and institutional officials seeking review of a radiology department.