Histopathology Scoring Systems of Stenosis Associated With Small Bowel Crohn's Disease: A Systematic Review.

BACKGROUND & AIMS: Stenosis is a common complication of Crohn's disease (CD) that has no effective medical therapy. Development of antifibrotic agents will require testing in randomized controlled trials. Computed tomography enterography- and magnetic resonance enterography-based technologies might be used to measure outcomes in these trials. These approaches have been validated in studies of patients with symptomatic strictures who underwent imaging evaluations followed by resection with histopathologic grading of the intestinal tissue for inflammation and/or fibrosis (the reference standard). Imaging findings have correlated with findings from quantitative or semiquantitative histologic evaluation of the degree of fibromuscular stenosis and/or inflammation on the resection specimen. However, it is not clear whether histologic findings are an accurate reference standard. We performed a systematic review of all published histologic scoring systems used to assess stenosing CD. METHODS: We performed a comprehensive search of Embase and MEDLINE of studies through March 13, 2019, that used a histologic scoring system to characterize small bowel CD and assessed inflammatory and fibrotic alterations within the same adult individual. All scores fitting the criteria were included in our analysis, independent of the presence of stricturing disease, as long as inflammation and fibrosis were evaluated separately but in the same scoring system. RESULTS: We observed substantial heterogeneity among the scoring systems, which were not derived from modern principles for evaluative index development. None had undergone formal validity or reliability testing. None of the existing indices had been constructed according to accepted methods for the development of evaluative indices. Basic knowledge regarding their operating properties were lacking. Specific indices for evaluating the important pathologic component of myofibroblast hypertrophy or hyperplasia have not been proposed. CONCLUSIONS: In a systematic review of publications, we found a lack of validated histopathologic scoring systems for assessment of fibromuscular stenosis. Data that describe the operating properties of existing cross-sectional imaging techniques for stenosing CD should be questioned. Development and validation of a histopathology index is an important research priority.

Temporal Trends in the Incidence and Natural History of Diverticulitis: A Population-Based Study.

OBJECTIVES: Data on the incidence and natural history of diverticulitis are largely hospital-based and exclude the majority of diverticulitis patients, who are treated in an outpatient setting for uncomplicated diverticulitis. We assessed temporal trends in the epidemiology of diverticulitis in the general population. METHODS: Through the Rochester Epidemiology Project we reviewed the records of all individuals with a diagnosis of diverticulitis from 1980 to 2007 in Olmsted County, Minnesota, USA. RESULTS: In 1980-1989, the incidence of diverticulitis was 115/100,000 person-years, which increased to 188/100,000 in 2000-2007 (P<0.001). Incidence increased with age (P<0.001); however, the temporal increase was greater in younger people (P<0.001). Ten years after the index and second diverticulitis episodes, 22% and 55% had a recurrence, respectively. This recurrence rate was greater in younger people (hazard ratio (HR) per decade 0.63; 95% confidence interval (CI), 0.59-0.66) and women (HR 0.68; 95% CI, 0.58-0.80). Complications were seen in 12%; this rate did not change over time. Recurrent diverticulitis was associated with a decreased risk of complications (P<0.001). Age was associated with increased risk of local (odds ratio (OR) 1.27 per decade; 95% CI, 1.04-1.57) and systemic (OR 1.83; 95% CI, 1.20-2.80) complications. Survival after diverticulitis was lower in older people (P<0.001) and men (P<0.001) and worsened over time (P<0.001). The incidence of surgery for diverticulitis did not change from 1980 to 2007. CONCLUSIONS: The incidence of diverticulitis has increased by 50% in 2000-2007 compared with 1990-1999, and more so in younger people. Complications are relatively uncommon. Recurrent diverticulitis is frequent but typically uncomplicated. Younger people with diverticulitis have less severe disease, more recurrence, and better survival.

CT colonography for the detection of nonpolypoid adenomas: sensitivity assessed with restricted national CT colonography trial criteria.

OBJECTIVE: The purpose of this study was to determine the prevalence of nonpolypoid adenomas and the sensitivity of CT colonography (CTC) in their detection by use of the restricted criteria of height-to-width ratio<50% and height elevation≤3 mm. MATERIALS AND METHODS: In the National CT Colonography Trial (American College of Radiology Imaging Network protocol 6664), a cohort of 2531 participants without symptoms underwent CTC and screening colonoscopy. The CTC examinations were interpreted with both 2D and 3D techniques. Nonpolypoid adenomatous polyps identified with CTC or colonoscopy were retrospectively reviewed to determine which polyps met the restricted criteria. The prevalence of nonpolypoid adenomas and the prospective sensitivity of CTC were determined. Descriptive statistics were used to report the prevalence, size, and histologic features. The sensitivities (with 95% CIs) for nonpolypoid and polypoid lesions were compared by two-sided Z test for independent binomial proportions. RESULTS: The retrospective review confirmed 21 nonpolypoid adenomas, yielding a prevalence of 0.83% (21 of 2531 participants). Eight (38.1%) were advanced adenomas, many (50% [4/8]) only because of large size (≥10 mm). The overall per polyp sensitivity of CTC (combined 2D and 3D interpretation) for detecting nonpolypoid adenomas≥5 mm (n=21) was 0.76; ≥6 mm (n=16), 0.75; and ≥10 mm (n=5), 0.80. These values were not statistically different from the sensitivity of detecting polypoid adenomas (p>0.37). CONCLUSION: In this large screening population, nonpolypoid adenomas had a very low prevalence (<1%), and advanced pathologic features were uncommon in polyps<10 mm in diameter. Most nonpolypoid adenomas are technically visible at CTC. The prospective sensitivity is similar to that for polypoid adenomas when the interpretation combines both 2D and 3D review.

Case-control study to estimate the performance of dual-energy computed tomography for anterior cruciate ligament tears in patients with history of knee trauma.

OBJECTIVE: Computed tomography (CT) is used to assess for fracture after knee trauma, but identification of ligamentous injuries may also be beneficial. Our purpose is to assess the potential of dual-energy computed tomography (DECT) for the detection of complete anterior cruciate ligament (ACL) disruption. METHODS: Sixteen patients with unilateral traumatic ACL disruption (average of 58 days following trauma) confirmed by MRI, and 11 control patients without trauma, underwent DECT of both knees. For each knee, axial, sagittal, and oblique sagittal images (with DECT bone removal, single-energy (SE) bone removal, and DECT tendon-specific color mapping) were reconstructed. Four musculoskeletal radiologists randomly evaluated the 324 DECT reconstructed series (54 knees with 6 displays) separately, to assess for ACL disruption using a five-point scale (1 = definitely not torn, to 5 = definitely torn). ROC analysis was used to compare performance across readers and displays. RESULTS: Sagittal oblique displays (mixed kV soft tissue, SE bone removal, and DECT bone removal) demonstrated higher areas under the curve for ACL disruption (AUC = 0.95, 0.93 and 0.95 respectively) without significant differences in performance between readers (p > 0.23). Inter-reader agreement was also better for these display methods (ICC range 0.62-0.69) compared with other techniques (ICC range 0.41-0.57). Mean sensitivity for ACL disruption was worst for DECT tendon-specific color map and axial images (24 % and 63 % respectively). CONCLUSION: DECT knee images with oblique sagittal reconstructions using either mixed kV or bone removal displays (either DECT or SE) depict ACL disruption in the subacute or chronic setting with reliable identification by musculoskeletal radiologists.

Dynamic ileal pouch emptying studies.

Although much radiologic literature has focused on the short-term post-operative complications associated with ileal pouches, as the number of patients with long-term pouches has grown, there is increasing realization of the functional deficits that may occur long after pouch creation. Dynamic pouch imaging using fluoroscopy and MRI can provide assessment of the underlying causes of symptomatic pouch dysfunction and can provide critical insight to the management of this complex patient population. In this paper, we provide an overview of the unique problems encountered in patients with long-term ileal pouches, and provide an overview of the techniques, interpretation, and reporting for fluoroscopic and MR pouch defecography.

Obstetric trauma, pelvic floor injury and fecal incontinence: a population-based case-control study.

OBJECTIVES: Current concepts based on referral center data suggest that pelvic floor injury from obstetric trauma is a major risk factor for fecal incontinence (FI) in women. In contrast, a majority of community women only develop FI decades after vaginal delivery, and obstetric events are not independent risk factors for FI. However, obstetric events are imperfect surrogates for anal and pelvic floor injury, which is often clinically occult. Hence, the objectives of this study were to evaluate the relationship between prior obstetric events, pelvic floor injury, and FI among community women. METHODS: In this nested case-control study of 68 women with FI (cases; mean age 57 years) and 68 age-matched controls from a population-based cohort in Olmsted County, MN, pelvic floor anatomy and motion during voluntary contraction and defecation were assessed by magnetic resonance imaging. Obstetric events and bowel habits were recorded. RESULTS: By multivariable analysis, internal sphincter injury (cases-28%, controls-6%; odds ratio (OR): 8.8; 95% confidence interval (CI): 2.3-34) and reduced perineal descent during defecation (cases-2.6 ± 0.2 cm, controls-3.1 ± 0.2 cm; OR: 1.7; 95% CI: 1.2-2.4) increased FI risk, but external sphincter injury (cases-25%, controls-4%; P<0.005) was not independently predictive. Puborectalis injury was associated (P<0.05) with impaired anorectal motion during squeeze, but was not independently associated with FI. Grades 3-4 episiotomy (OR: 3.9; 95% CI: 1.4-11) but not other obstetric events increased the risk for pelvic floor injury. Heavy smoking (≥ 20 pack-years) was associated (P=0.052) with external sphincter atrophy. CONCLUSIONS: State-of-the-art imaging techniques reveal pelvic floor injury or abnormal anorectal motion in a minority of community women with FI. Internal sphincter injury and reduced perineal descent during defecation are independent risk factors for FI. In addition to grades 3-4 episiotomy, smoking may be a potentially preventable, risk factor for pelvic floor injury.

A New Frontier in Temporal Bone Imaging: Photon-Counting Detector CT Demonstrates Superior Visualization of Critical Anatomic Structures at Reduced Radiation Dose.

BACKGROUND AND PURPOSE: Photon-counting detector CT is a new technology with a limiting spatial resolution of ≤150 µm. In vivo comparisons between photon-counting detector CT and conventional energy-integrating detector CT are needed to determine the clinical impact of photon counting-detector CT in temporal bone imaging. MATERIALS AND METHODS: Prospectively recruited patients underwent temporal bone CT examinations on an investigational photon-counting detector CT system after clinically indicated temporal bone energy-integrating detector CT. Photon-counting detector CT images were obtained at an average 31% lower dose compared with those obtained on the energy-integrating detector CT scanner. Reconstructed images were evaluated in axial, coronal, and Pöschl planes using the smallest available section thickness on each system (0.4 mm on energy-integrating detector CT; 0.2 mm on photon-counting detector CT). Two blinded neuroradiologists compared images side-by-side and scored them using a 5-point Likert scale. A post hoc reassignment of readers' scores was performed so that the scores reflected photon-counting detector CT performance relative to energy-integrating detector CT. RESULTS: Thirteen patients were enrolled, resulting in 26 image sets (left and right sides). The average patient age was 63.6 [SD, 13.4] years; 7 were women. Images from the photon-counting detector CT scanner were significantly preferred by the readers in all reconstructed planes (P < .001). Photon-counting detector CT was rated superior for the evaluation of all individual anatomic structures, with the oval window (4.79) and incudostapedial joint (4.75) receiving the highest scores on a Likert scale of 1-5. CONCLUSIONS: Temporal bone CT images obtained on a photon-counting detector CT scanner were rated as having superior spatial resolution and better critical structure visualization than those obtained on a conventional energy-integrating detector scanner, even with a substantial dose reduction.

Dual-energy CT iodine overlay technique for characterization of renal masses as cyst or solid: a phantom feasibility study.

The aim of this study was to assess the ability of dual-energy computed tomography (DECT) to classify phantom renal lesions as cysts or enhancing masses. Six cylinders ranging in diameter from 0.5 to 3.0 cm were filled with distilled water or titrated iodinated contrast solutions with CT attenuation values at 120 kVp of 0 Hounsfield units (HU) for a cyst proxy or 10, 20, or 40 HU to represent enhancing masses. These were placed in a 12-cm-diameter renal phantom containing puréed beef mixed with iodinated contrast medium to simulate enhancing renal parenchyma of 100 and 250 HU and submerged within a 28-cm water bath. These combinations produced 48 individual phantom renal lesions of differing sizes, internal and parenchymal enhancement (12 cysts and 36 enhancing masses). DECT using 80 and 140 kVp was performed on a dual-source CT scanner. Commercial software created a color-encoded overlay indicating the location of iodine within the phantom. The lesions were individually graded as a cyst or enhancing mass by blinded, consensus interpretation of two genitourinary radiologists. Thirty-five of 36 enhancing masses and 10/12 cysts were correctly identified, equating to a sensitivity and specificity of 97% (95% CI 84-100%) and 83% (95% CI 51-97%), respectively. All lesions of 20- and 40-HU enhancement and 92% of 10-HU lesions were identified correctly. In a phantom model, the DECT iodine overlay technique is highly sensitive in detecting enhancing renal masses. Refinement of the technique remains necessary to improve specificity. If validated in patients, this may obviate the need for unenhanced acquisitions for renal mass characterization.

CT enterography technique: theme and variations.

CT enterography has rapidly gained acceptance as a method for visualizing the small bowel lumen, wall and mesentery for a variety of clinical indications. Focusing on the identification of Crohn's disease, and vascular and neoplastic small bowel masses, this review summarizes oral contrast agents and CT acquisition techniques used for CT enterography, alternatives that can be used to tailor the exam for specific indications, and how such variations affect the appearance of a variety of pathologies at CT imaging.

Evaluation of Lower-Dose Spiral Head CT for Detection of Intracranial Findings Causing Neurologic Deficits.

BACKGROUND AND PURPOSE: Despite the frequent use of unenhanced head CT for the detection of acute neurologic deficit, the radiation dose for this exam varies widely. Our aim was to evaluate the performance of lower-dose head CT for detection of intracranial findings resulting in acute neurologic deficit. MATERIALS AND METHODS: Projection data from 83 patients undergoing unenhanced spiral head CT for suspected neurologic deficits were collected. Cases positive for infarction, intra-axial hemorrhage, mass, or extra-axial hemorrhage required confirmation by histopathology, surgery, progression of findings, or corresponding neurologic deficit; cases negative for these target diagnoses required negative assessments by two neuroradiologists and a clinical neurologist. A routine dose head CT was obtained using 250 effective mAs and iterative reconstruction. Lower-dose configurations were reconstructed (25-effective mAs iterative reconstruction, 50-effective mAs filtered back-projection and iterative reconstruction, 100-effective mAs filtered back-projection and iterative reconstruction, 200-effective mAs filtered back-projection). Three neuroradiologists circled findings, indicating diagnosis, confidence (0-100), and image quality. The difference between the jackknife alternative free-response receiver operating characteristic figure of merit at routine and lower-dose configurations was estimated. A lower 95% CI estimate of the difference greater than -0.10 indicated noninferiority. RESULTS: Forty-two of 83 patients had 70 intracranial findings (29 infarcts, 25 masses, 10 extra- and 6 intra-axial hemorrhages) at routine head CT (CT dose index = 38.3 mGy). The routine-dose jackknife alternative free-response receiver operating characteristic figure of merit was 0.87 (95% CI, 0.81-0.93). Noninferiority was shown for 100-effective mAs iterative reconstruction (figure of merit difference, -0.04; 95% CI, -0.08 to 0.004) and 200-effective mAs filtered back-projection (-0.02; 95% CI, -0.06 to 0.02) but not for 100-effective mAs filtered back-projection (-0.06; 95% CI, -0.10 to -0.02) or lower-dose levels. Image quality was better at higher-dose levels and with iterative reconstruction (P < .05). CONCLUSIONS: Observer performance for dose levels using 100-200 eff mAs was noninferior to that observed at 250 effective mAs with iterative reconstruction, with iterative reconstruction preserving noninferiority at a mean CT dose index of 15.2 mGy.

Incidental findings in CT colonography: literature review and survey of current research practice.

Incidental findings (IFs) of potential medical significance are seen in approximately 5-8 percent of asymptomatic subjects and 16 percent of symptomatic subjects participating in large computed tomography (CT) colonography (CTC) studies, with the incidence varying further by CT acquisition technique. While most CTC research programs have a well-defined plan to detect and disclose IFs, such plans are largely communicated only verbally. Written consent documents should also inform subjects of how IFs of potential medical significance will be detected and reported in CTC research studies.

Normal values for assessment of anal sphincter morphology, anorectal motion, and pelvic organ prolapse with MRI in healthy women.

BACKGROUND: Endoanal MRI and MR defecography are used to identify anal sphincter injury and disordered defecation. However, few studies have evaluated findings in asymptomatic healthy people. The effects of BMI and parity on rectoanal motion and evacuation are unknown. METHODS: In 113 asymptomatic females (age 50 ± 17 years, Mean ± SD) without risk factors for anorectal trauma, anal sphincter appearance, anorectal motion, and pelvic organ prolapse were evaluated with MRI. The relationship between age, BMI, and parity and structural findings were evaluated with parametric and non-parametric tests. RESULTS: The anal sphincters and puborectalis appeared normal in over 90% of women. During dynamic MRI, the anorectal angle was 100 ± 1º (Mean ± SEM) at rest, 70 ± 2° at squeeze, and 120 ± 2° during defecation. The change in anorectal angle during squeeze (r = -.25, P < .005), but not during evacuation (r = .13, P = .25) was associated with age. In the multivariable models, BMI (P < .01) and parity (P < .01) were, respectively, independently associated with the intersubject variation in the anorectal angle at rest and the angle change during squeeze. Ten percent or fewer women had had descent of the bladder base or uterus 4 cm or more below the pubococcygeal line or a rectocele measuring 4 cm or larger. Only 5% had a patulous anal canal. CONCLUSIONS: In addition to age, BMI and parity also affect anorectal motion in asymptomatic women. These findings provide age-adjusted normal values for rectoanal anatomy and pelvic floor motion.

Low kV versus dual-energy virtual monoenergetic CT imaging for proven liver lesions: what are the advantages and trade-offs in conspicuity and image quality? A pilot study.

PURPOSE: Single-energy low tube potential (SE-LTP) and dual-energy virtual monoenergetic (DE-VM) CT images both increase the conspicuity of hepatic lesions by increasing iodine signal. Our purpose was to compare the conspicuity of proven liver lesions, artifacts, and radiologist preferences in dose-matched SE-LTP and DE-VM images. METHODS: Thirty-one patients with 72 proven liver lesions (21 benign, 51 malignant) underwent full-dose contrast-enhanced dual-energy CT (DECT). Half-dose images were obtained using single tube reconstruction of the dual-source SE-LTP projection data (80 or 100 kV), and by inserting noise into dual-energy projection data, with DE-VM images reconstructed from 40 to 70 keV. Three blinded gastrointestinal radiologists evaluated half-dose SE-LTP and DE-VM images, ranking and grading liver lesion conspicuity and diagnostic confidence (4-point scale) on a per-lesion basis. Image quality (noise, artifacts, sharpness) was evaluated, and overall image preference was ranked on per-patient basis. Lesion-to-liver contrast-to-noise ratio (CNR) was compared between techniques. RESULTS: Mean lesion size was 1.5 ± 1.2 cm. Across the readers, the mean conspicuity ratings for 40, 45, and 50 keV half-dose DE-VM images were superior compared to other half-dose image sets (p < 0.0001). Per-lesion diagnostic confidence was similar between half-dose SE-LTP compared to half-dose DE-VM images (p ≥ 0.05; 1.19 vs. 1.24-1.32). However, SE-LTP images had less noise and artifacts and were sharper compared to DE-VM images less than 70 keV (p < 0.05). On a per-patient basis, radiologists preferred SE-LTP images the most and preferred 40-50 keV the least (p < 0.0001). Lesion CNR was also higher in SE-LTP images than DE-VM images (p < 0.01). CONCLUSION: For the same applied dose level, liver lesions were more conspicuous using DE-VM compared to SE-LTP; however, SE-LTP images were preferred more than any single DE-VM energy level, likely due to lower noise and artifacts.

An expert consensus to standardise definitions, diagnosis and treatment targets for anti-fibrotic stricture therapies in Crohn's disease.

BACKGROUND: Fibrotic stricture is a common complication of Crohn's disease (CD) affecting approximately half of all patients. No specific anti-fibrotic therapies are available; however, several therapies are currently under evaluation. Drug development for the indication of stricturing CD is hampered by a lack of standardised definitions, diagnostic modalities, clinical trial eligibility criteria, endpoints and treatment targets in stricturing CD. AIM: To standardise definitions, diagnosis and treatment targets for anti-fibrotic stricture therapies in Chron's disease. METHODS: An interdisciplinary expert panel consisting of 15 gastroenterologists and radiologists was assembled. Using modified RAND/University of California Los Angeles appropriateness methodology, 109 candidate items derived from systematic review and expert opinion focusing on small intestinal strictures were anonymously rated as inappropriate, uncertain or appropriate. Survey results were discussed as a group before a second and third round of voting. RESULTS: Fibrotic strictures are defined by the combination of luminal narrowing, wall thickening and pre-stenotic dilation. Definitions of anastomotic (at site of prior intestinal resection with anastomosis) and naïve small bowel strictures were similar; however, there was uncertainty regarding wall thickness in anastomotic strictures. Magnetic resonance imaging is considered the optimal technique to define fibrotic strictures and assess response to therapy. Symptomatic strictures are defined by abdominal distension, cramping, dietary restrictions, nausea, vomiting, abdominal pain and post-prandial abdominal pain. Need for intervention (endoscopic balloon dilation or surgery) within 24-48 weeks is considered the appropriate endpoint in pharmacological trials. CONCLUSIONS: Consensus criteria for diagnosis and response to therapy in stricturing Crohn's disease should inform both clinical practice and trial design.

Polyp measurement with CT colonography: multiple-reader, multiple-workstation comparison.

OBJECTIVE: The risk of invasive colorectal cancer in colorectal polyps correlates with lesion size. Our purpose was to define the most accurate methods for measuring polyp size at CT colonography (CTC) using three models of workstations and multiple observers. MATERIALS AND METHODS: Six reviewers measured 24 unique polyps of known size (5, 7, 10, and 12 mm), shape (sessile, flat, and pedunculated), and location (straight or curved bowel segment) using CTC data sets obtained at two doses (5 mAs and 65 mAs) and a previously described colonic phantom model. Reviewers measured the largest diameter of polyps on three proprietary workstations. Each polyp was measured with lung and soft-tissue windows on axial, 2D multiplanar reconstruction (MPR), and 3D images. RESULTS: There were significant differences among measurements obtained at various settings within each workstation (p < 0.0001). Measurements on 2D images were more accurate with lung window than with soft-tissue window settings (p < 0.0001). For the 65-mAs data set, the most accurate measurements were obtained in analysis of axial images with lung window, 2D MPR images with lung window, and 3D tissue cube images for Wizard, Advantage, and Vitrea workstations, respectively, without significant differences in accuracy among techniques (0.11 < p < 0.59). The mean absolute error values for these optimal settings were 0.48 mm, 0.61 mm, and 0.76 mm, respectively, for the three workstations. Within the ultralow-dose 5-mAs data set the best methods for Wizard, Advantage, and Vitrea were axial with lung window, 2D MPR with lung window, and 2D MPR with lung window, respectively. Use of nearly all measurement methods, except for the Vitrea 3D tissue cube and the Wizard 2D MPR with lung window, resulted in undermeasurement of the true size of the polyps. CONCLUSION: Use of CTC computer workstations facilitates accurate polyp measurement. For routine CTC examinations, polyps should be measured with lung window settings on 2D axial or MPR images (Wizard and Advantage) or 3D images (Vitrea). When these optimal methods are used, these three commercial workstations do not differ significantly in acquisition of accurate polyp measurements at routine dose settings.

Comparative performance of two polyp detection systems on CT colonography.

OBJECTIVE: The purpose of our study was to evaluate two current automatic polyp detection systems to determine their sensitivity and false-positive rate in patients who have undergone CT colonography and subsequent endoscopy. MATERIALS AND METHODS: We evaluated two polyp detection systems--Polyp Enhanced Viewing (PEV) and the Summers computer-aided detection (CAD) system (National Institutes of Health [NIH]) using a unique cohort of CT colonography examinations: 31 examinations with true-positive lesions identified by radiologists and 34 examinations with false-positive lesions incorrectly identified by radiologists. All patients had reference-standard colonoscopy within 7 days of CT. Candidate lesions were compared with the endoscopic reference standard and prospective radiologist interpretation. The sensitivity and false-positive rates were calculated for each system. RESULTS: The NIH system had a higher sensitivity than the PEV tool for polyps > or = 1 cm (22/23, 96%; 78-99%, 95% CI vs 14/23, 61%; 38-81%, 95% CI; p = 0.008, respectively). There was no significant difference in the detection of medium-sized polyps 6-9 mm in size (8/13 vs 6/13, p = 0.68, respectively). The PEV tool had an average of 1.18 false-positive detections per patient, whereas the NIH tool had an average of 5.20 false-positive detections per patient, with the PEV tool having significantly fewer false-positive detections in both patient groups (p < 0.001). CONCLUSION: One polyp detection system tended to operate with a higher sensitivity, whereas the other tended to operate with a lower false-positive rate. Prospective trials using polyp detection systems as a primary or secondary means of CT colonography interpretation appear warranted.

A virtual clinical trial using projection-based nodule insertion to determine radiologist reader performance in lung cancer screening CT.

Task-based image quality assessment using model observers is promising to provide an efficient, quantitative, and objective approach to CT dose optimization. Before this approach can be reliably used in practice, its correlation with radiologist performance for the same clinical task needs to be established. Determining human observer performance for a well-defined clinical task, however, has always been a challenge due to the tremendous amount of efforts needed to collect a large number of positive cases. To overcome this challenge, we developed an accurate projection-based insertion technique. In this study, we present a virtual clinical trial using this tool and a low-dose simulation tool to determine radiologist performance on lung-nodule detection as a function of radiation dose, nodule type, nodule size, and reconstruction methods. The lesion insertion and low-dose simulation tools together were demonstrated to provide flexibility to generate realistically-appearing clinical cases under well-defined conditions. The reader performance data obtained in this virtual clinical trial can be used as the basis to develop model observers for lung nodule detection, as well as for dose and protocol optimization in lung cancer screening CT.

Low-Dose CT for Craniosynostosis: Preserving Diagnostic Benefit with Substantial Radiation Dose Reduction.

BACKGROUND AND PURPOSE: Given the positive impact of early intervention for craniosynostosis, CT is often performed for evaluation but radiation dosage remains a concern. We evaluated the potential for substantial radiation dose reduction in pediatric patients with suspected craniosynostosis. MATERIALS AND METHODS: CT projection data from pediatric patients undergoing head CT for suspected craniosynostosis were archived. Simulated lower-dose CT images corresponding to 25%, 10%, and 2% of the applied dose were created using a validated method. Three neuroradiologists independently interpreted images in a blinded, randomized fashion. All sutures were evaluated by using 3D volume-rendered images alone, and subsequently with 2D and 3D images together. Reference standards were defined by reader agreement by using routine dose and 2D and 3D images. Performance figures of merit were calculated based on reader response and confidence. RESULTS: Of 33 pediatric patients, 21 had craniosynostosis (39 positive sutures and 225 negative sutures). The mean volume CT dose index was 15.5 ± 2.3 mGy (range, 9.69-19.38 mGy) for the routine dose examination. Average figures of merit for multireader analysis ranged from 0.92 (95% CI, 0.90-0.95) at routine pediatric dose to 0.86 (95% CI, 0.79-0.94) at 2% dose using 3D images alone. Similarly, pooled reader figures of merit ranged from 0.91 (95% CI, 0.89-0.95) at routine pediatric dose to 0.85 (95% CI, 0.76-0.95) at 2% dose using 2D and 3D images together. At 25% and 10% dose, 95% CI of the difference in figures of merit from routine dose included 0, suggesting similar or noninferior performance. CONCLUSIONS: For pediatric head CT for evaluation of craniosynostosis, dose reductions of 75%-90% were possible without compromising observer performance.

Selective cytotoxicity of low-density lipoprotein to helper T cells of cutaneous T-cell lymphoma after photoperoxidation with 8-methoxypsoralen.

Lymphocyte-containing plasma subjected to photolysis in the presence of 8-methoxypsoralen (methoxsalen, 8-MOP) has previously been shown to be effective against cutaneous T-cell lymphoma and the AIDS-related complex. The mechanism of this effect was thought to involve photoreaction of 8-MOP with DNA, based on certain in vitro experiments. The results of this study suggest a different mechanism. Low-density lipoprotein (LDL) from fresh human plasma was photosensitized by addition of 8-MOP and exposure to UV light (mp-LDL), and the reactions of the LDL lipids and the chemical actions induced by these reactions were monitored. In a separate procedure, LDL was peroxidized with hydrogen peroxide and peroxidase (p-LDL). mp-LDL and p-LDL were then tested in cytotoxicity assays on HuT-78 helper T cells of cutaneous T-cell lymphoma. These results indicate that (a) LDL in plasma in the presence of very low concentrations of 8-MOP (200 ng/mL) can be peroxidized by UV light; (b) this photoperoxidized LDL is cytotoxic to helper T cells of cutaneous T-cell lymphoma in a dose-dependent manner; but (c) it does not kill normal lymphocytes under similar conditions. The findings also suggest alternative therapeutic strategies for treatment of cutaneous T-cell lymphoma, such as direct utilization of peroxidized LDL.

Cell death induced by peroxidized low-density lipoprotein: endopepsis.

Peroxidized low-density lipoprotein (p-LDL) has been previously demonstrated to be preferentially cytotoxic to certain malignant cells compared to normal cells of the same type. We present evidence that p-LDL is at least partially taken up through the LDL receptor and that it becomes localized in lysosomes. The integrity of lysosomes of p-LDL-treated cells is compromised, and leakage of their contents into the cytosol occurs. This leakage occurs early and precedes mitochondrial dysfunction. Brefeldin A inhibits this leakage, perhaps by interfering with the traffic between endosomes and lysosomes. Electron micrographs taken at various times suggest a mechanism of cell death which resembles certain aspects of the broad definition of apoptosis. However, we suggest that the cell death observed following p-LDL-induced release of lysosomal contents is essentially unique, with released lysosomal enzymes degrading the cell from within. We suggest that this process should be described as endopepsis.