Magnetic resonance imaging of the extensor mechanism.

Anterior knee pain is associated with many different causes. The clinical diagnosis may be unclear when the patient initially presents for evaluation. Magnetic resonance (MR) imaging is a valuable modality with high diagnostic accuracy in the evaluation of extensor mechanism pathology, which commonly presents with anterior knee pain. The most common disorders include patellar fracture, patellofemoral tracking abnormalities, tendon trauma and degeneration. These injuries manifest with characteristic patterns on MR imaging. This article discusses normal anatomy, common injuries, and diagnostic pitfalls on MR imaging.

WaveCNV: allele-specific copy number alterations in primary tumors and xenograft models from next-generation sequencing.

MOTIVATION: Copy number variations (CNVs) are a major source of genomic variability and are especially significant in cancer. Until recently microarray technologies have been used to characterize CNVs in genomes. However, advances in next-generation sequencing technology offer significant opportunities to deduce copy number directly from genome sequencing data. Unfortunately cancer genomes differ from normal genomes in several aspects that make them far less amenable to copy number detection. For example, cancer genomes are often aneuploid and an admixture of diploid/non-tumor cell fractions. Also patient-derived xenograft models can be laden with mouse contamination that strongly affects accurate assignment of copy number. Hence, there is a need to develop analytical tools that can take into account cancer-specific parameters for detecting CNVs directly from genome sequencing data. RESULTS: We have developed WaveCNV, a software package to identify copy number alterations by detecting breakpoints of CNVs using translation-invariant discrete wavelet transforms and assign digitized copy numbers to each event using next-generation sequencing data. We also assign alleles specifying the chromosomal ratio following duplication/loss. We verified copy number calls using both microarray (correlation coefficient 0.97) and quantitative polymerase chain reaction (correlation coefficient 0.94) and found them to be highly concordant. We demonstrate its utility in pancreatic primary and xenograft sequencing data. AVAILABILITY AND IMPLEMENTATION: Source code and executables are available at https://github.com/WaveCNV. The segmentation algorithm is implemented in MATLAB, and copy number assignment is implemented Perl. CONTACT: lakshmi.muthuswamy@gmail.com SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Magnetic resonance imaging of pediatric pelvic masses.

Both benign and malignant pelvic masses are encountered in the pediatric population. Although ultrasonography remains the modality of choice for initial evaluation of a pediatric pelvic mass, in selected cases magnetic resonance (MR) imaging can add important diagnostic information. MR imaging has several advantages over ultrasonography and computed tomography, including superior contrast resolution and an ability to characterize abnormalities based on unique tissue characteristics. MR evaluation assists in lesion characterization, presurgical planning, and staging when a malignancy is suspected. MR imaging also offers a nonionizing imaging modality for long-term follow-up of patients undergoing therapy for malignant pelvic masses.

Musculoskeletal ultrasound of the upper extremity in children.

Musculoskeletal US is becoming more widely performed in children. Although overlap between pediatric and adult pathology exists, particularly in older children who have a more mature skeleton, there are significant differences when assessing patients who have cartilaginous ossification centers, particularly in the context of trauma. Lack of ionizing radiation and dynamic imaging capabilities are significant advantages compared to CT and MRI. Although MRI provides excellent evaluation of soft tissues, the need for general anesthesia in a subset of patients is undesirable, particularly when US can provide similar information. Radiography is the primary modality to evaluate trauma; however, musculoskeletal US can be useful to assess alignment of unossified structures, fractures that extend to involve the unossified epiphyses, occult fractures, physeal separation, presence of intra-articular bodies (particularly those that are not ossified), ligamentous injury and the occasionally encountered periosteum trapped between fracture fragments. The purpose of this article is to review commonly encountered pathologies unique to the pediatric upper extremities that are ideally imaged with sonography. Some pathology that overlaps with the adult population such as infection and sports injuries are briefly covered.

Imaging review of skeletal tumors of the pelvis malignant tumors and tumor mimics.

Malignant lesions of the pelvis are not uncommon and need to be differentiated from benign lesions and tumor mimics. Appearances are sometimes nonspecific leading to consideration of a broad differential diagnosis. Clinical history, anatomic location, and imaging characterization can help narrow the differential diagnosis. The focus of this paper is to demonstrate the imaging features and the role of plain films, computed tomography, and magnetic resonance imaging for detecting and characterizing malignant osseous pelvic lesions and their common mimics.

A critical evaluation of US for the diagnosis of pediatric acute appendicitis in a real-life setting: how can we improve the diagnostic value of sonography?

BACKGROUND: We have observed that day-to-day use of US for acute appendicitis does not perform as well as described in the literature. OBJECTIVE: Review the diagnostic performance of US in acute appendicitis with attention to factors that influence performance. MATERIALS AND METHODS: Retrospective review of all sonograms for acute appendicitis in children from May 2005 to May 2010 with attention to the rate of identification of the appendix, training of personnel involved and diagnostic accuracy. RESULTS: The appendix was identified in 246/1,009 cases (24.4%), with identification increasing over time. The accuracy of US was 85-91% with 35 false-positives and 54 false-negatives. Pediatric sonographers were significantly better at identifying the appendix than non-pediatric sonographers (P < 0.0001). Increased weight was the only patient factor that influenced identification of the appendix (P = 0.006). CT use was stable over the 5 years but declined in cases where the appendix was identified by US. CONCLUSION: In day-to-day use, US does not perform as purported in the literature. We do not visualize the appendix as often as we should and false-negative and false-positive exams are too common. To improve the diagnostic performance of this modality, involvement by experienced personnel and/or additional training is needed.

Diffuse uterine leiomyomatosis in a child.

Leiomyomas are the most common benign uterine tumor; however, this entity is relatively uncommon in the pediatric population. Although leiomyomas most commonly present as solitary uterine masses, unusual patterns of growth have been described including diffuse leiomyomatosis. In this condition, the myometrium of the uterus is symmetrically expanded by innumerable confluent leiomyomas; this pattern of growth is quite uncommon and has never been reported in a pediatric patient. This case report illustrates the imaging appearance of diffuse uterine leiomyomatosis in an otherwise healthy 16-year-old girl.

Rare de novo and transmitted copy-number variation in autistic spectrum disorders.

To explore the genetic contribution to autistic spectrum disorders (ASDs), we have studied genomic copy-number variation in a large cohort of families with a single affected child and at least one unaffected sibling. We confirm a major contribution from de novo deletions and duplications but also find evidence of a role for inherited "ultrarare" duplications. Our results show that, relative to males, females have greater resistance to autism from genetic causes, which raises the question of the fate of female carriers. By analysis of the proportion and number of recurrent loci, we set a lower bound for distinct target loci at several hundred. We find many new candidate regions, adding substantially to the list of potential gene targets, and confirm several loci previously observed. The functions of the genes in the regions of de novo variation point to a great diversity of genetic causes but also suggest functional convergence.

MRI of the pediatric knee.

OBJECTIVE: The purpose of this article is to describe findings on MRI in the evaluation of knee injury in pediatric patients. CONCLUSION: Injury patterns in the pediatric knee overlap and differ from adults. Differences include open physes, changing mechanics, and differences in ligamentous support. Awareness of normal variants, common incidental findings, and normal evolution of bone marrow aid in the interpretation.

MRI of vulvar Crohn disease.

Crohn disease is a chronic granulomatous inflammatory disorder that most commonly affects the gastrointestinal tract, particularly the distal small bowel and colon. While certain extraintestinal manifestations of Crohn disease are relatively common and well-known, others, such as metastatic cutaneous involvement, are quite rare and may be difficult to recognize, particularly in the pediatric population. This case report illustrates the magnetic resonance imaging (MRI) appearance of vulvar region cutaneous Crohn disease in an 11-year-old girl.

MRI of congenital urethroperineal fistula.

We present the MRI features of a congenital urethroperineal fistula diagnosed in a 12-year-old boy being evaluated after a single urinary tract infection. This diagnosis was initially suggested by voiding cystourethrogram and confirmed by MRI. Imaging revealed an abnormal fluid-filled tract arising from the posterior urethra and tracking to the perineal skin surface that increased in size during micturition. Surgical resection and histopathological evaluation of the abnormal tract confirmed the diagnosis of congenital urethroperineal fistula. MRI played important roles in confirming the diagnosis and assisting surgical planning.

CT appearances following laparoscopic partial nephrectomy for renal cell carcinoma using a rolled cellulose bolster.

PURPOSE: To describe the evolving computed tomography (CT) appearances of a cellulose surgical bolster used as a hemostatic agent in patients who undergo laparoscopic partial nephrectomy for renal cell carcinoma. MATERIALS AND METHODS: We retrospectively reviewed the follow-up CT studies of 33 patients with stage T1N0M0 renal carcinoma who underwent laparoscopic partial nephrectomy using a rolled, oxidized, regenerated cellulose sheet sutured in place as a bolster in the parenchymal defect. Thirteen patients undergoing laparoscopic partial nephrectomy without the use of a bolster were also evaluated to differentiate imaging features. RESULTS: The bolster-related masses were significantly larger than those seen in the non-bolster patients. There was a decrease in size of the post-operative bolster-related mass with time. The bolster shape evolved with time, initially appearing oval, and becoming irregular with decreasing size. Equivocal increase in attenuation of 10-20 HU was seen in 6 patients. Increase in attenuation of greater than 20 HU was seen in 3 patients. There was no evidence of tumor recurrence in any of the patients. Invagination of fat was seen in two bolster-related masses at 18 months or greater. CONCLUSIONS: Cellulose bolster has a variable appearance on follow-up CT exams. Evolutionary features include reduction in bolster size and shape with time leading finally to non-visualization. Bolster enhancement can mimic abscesses and tumor recurrence.

Novel genomic alterations and clonal evolution in chronic lymphocytic leukemia revealed by representational oligonucleotide microarray analysis (ROMA).

We examined copy number changes in the genomes of B cells from 58 patients with chronic lymphocytic leukemia (CLL) by using representational oligonucleotide microarray analysis (ROMA), a form of comparative genomic hybridization (CGH), at a resolution exceeding previously published studies. We observed at least 1 genomic lesion in each CLL sample and considerable variation in the number of abnormalities from case to case. Virtually all abnormalities previously reported also were observed here, most of which were indeed highly recurrent. We observed the boundaries of known events with greater clarity and identified previously undescribed lesions, some of which were recurrent. We profiled the genomes of CLL cells separated by the surface marker CD38 and found evidence of distinct subclones of CLL within the same patient. We discuss the potential applications of high-resolution CGH analysis in a clinical setting.

Feature extraction using molecular planes for fuzzy relational clustering of a flexible dopamine reuptake inhibitor.

Six rigid-body parameters (Shift, Slide, Rise, Tilt, Roll, Twist) are commonly used to describe the relative displacement and orientation of successive base pairs in a nucleic acid structure. The present work adapts this approach to describe the relative displacement and orientation of any two planes in an arbitrary molecule-specifically, planes which contain important pharmacophore elements. Relevant code from the 3DNA software package (Nucleic Acids Res. 2003, 31, 5108-5121) was generalized to treat molecular fragments other than DNA bases as input for the calculation of the corresponding rigid-body (or "planes") parameters. These parameters were used to construct feature vectors for a fuzzy relational clustering study of over 700 conformations of a flexible analogue of the dopamine reuptake inhibitor, GBR 12909. Several cluster validity measures were used to determine the optimal number of clusters. Translational (Shift, Slide, Rise) rather than rotational (Tilt, Roll, Twist) features dominate clustering based on planes that are relatively far apart, whereas both types of features are important to clustering when the pair of planes are close by. This approach was able to classify the data set of molecular conformations into groups and to identify representative conformers for use as template conformers in future Comparative Molecular Field Analysis studies of GBR 12909 analogues. The advantage of using the planes parameters, rather than the combination of atomic coordinates and angles between molecular planes used in our previous fuzzy relational clustering of the same data set (J. Chem. Inf. Model. 2005, 45, 610-623), is that the present clustering results are independent of molecular superposition and the technique is able to identify clusters in the molecule considered as a whole. This approach is easily generalizable to any two planes in any molecule.

Strong association of de novo copy number mutations with autism.

We tested the hypothesis that de novo copy number variation (CNV) is associated with autism spectrum disorders (ASDs). We performed comparative genomic hybridization (CGH) on the genomic DNA of patients and unaffected subjects to detect copy number variants not present in their respective parents. Candidate genomic regions were validated by higher-resolution CGH, paternity testing, cytogenetics, fluorescence in situ hybridization, and microsatellite genotyping. Confirmed de novo CNVs were significantly associated with autism (P = 0.0005). Such CNVs were identified in 12 out of 118 (10%) of patients with sporadic autism, in 2 out of 77 (3%) of patients with an affected first-degree relative, and in 2 out of 196 (1%) of controls. Most de novo CNVs were smaller than microscopic resolution. Affected genomic regions were highly heterogeneous and included mutations of single genes. These findings establish de novo germline mutation as a more significant risk factor for ASD than previously recognized.

Sonographic evaluation of early-stage breast cancers that undergo neoadjuvant chemotherapy.

OBJECTIVE: We prospectively evaluated low-stage breast cancers treated with neoadjuvant chemotherapy using whole-volume sonography and color Doppler imaging. METHODS: Thirty-four women with breast cancer (mean maximum size, 2.4 cm) received neoadjuvant chemotherapy with doxorubicin and docetaxel. Targeted whole-volume sonography of tumor sites was performed before and after chemotherapy to assess mass size, color pixel speed-weighted density, and American College of Radiology Breast Imaging Reporting and Data System sonographic characteristics. After chemotherapy, tumor sites were excised by lumpectomy or mastectomy. RESULTS: Three (11.3%) of 34 patients had a complete histologic response. After chemotherapy, correlation was r = 0.716 between final histologic and sonographic sizes. Compared with histologic residual tumors, sonography had 4 false-negative results, 3 false-positive results, and 27 true-positive results (sensitivity, 87%), with no false-negative results among a subgroup of tumors of 7 mm and larger (sensitivity, 100%). The 3 cases with false-positive results were histologic fibrosis or biopsy changes. Mean speed-weighted density was 0.015 before and 0.0082 after chemotherapy (P = .03). After chemotherapy, vascularity was less common within (P = .06) or adjacent to (P = .009) masses or in tumor sites (P = .05). Prechemotherapy variables of gray scale characteristics and vascularity were compared with final histologic size, and all had P > .20. CONCLUSIONS: Postchemotherapy sensitivity of sonography was high for residual tumors of 7 mm or larger. Correlation was moderate between histologic and sonographic final tumor sizes. False-positive results were caused by fibrosis or biopsy-related changes. False-negative results occurred with residual tumor size of 6 mm or smaller. After chemotherapy, vascularity usually decreased, and this was not specific for complete response. Before chemotherapy, no vascular or gray scale feature at initial imaging predicted complete responders.