Imaging of Cystic Fibrosis and Pediatric Bronchiectasis.

1. CT is superior to pulmonary function tests and chest radiography for the assessment and monitoring of cystic fibrosis (CF)-related lung disease and, also, of pediatric bronchiectasis not caused by CF (hereafter referred to as non-CF bronchiectasis). 2. Low-dose CT protocols that impart radiation doses similar to those used in chest radiography are feasible for the surveillance of patients with bronchiectasis. 3. Chest radiography is still most commonly used as the first-line imaging examination of choice for the assessment of acute complications related to bronchiectasis. 4. Pulmonary MRI, with or without the use of inhaled hyperpolarized gas, can be performed to obtain functional information, and, in dedicated centers, it may yield imaging results comparable to those obtained by CT. 5. Gastrointestinal and pancreaticobiliary manifestations of CF are observed with greater frequency in adults, because of increased life expectancy.

Pure Iterative Reconstruction Improves Image Quality in Computed Tomography of the Abdomen and Pelvis Acquired at Substantially Reduced Radiation Doses in Patients With Active Crohn Disease.

UNLABELLED: We assessed diagnostic accuracy and image quality of modified protocol (MP) computed tomography (CT) of the abdomen and pelvis reconstructed using pure iterative reconstruction (IR) in patients with Crohn disease (CD). METHODS: Thirty-four consecutive patients with CD were referred with suspected extramural complications. Two contemporaneous CT datasets were acquired in all patients: standard protocol (SP) and MP. The MP and SP protocols were designed to impart radiation exposures of 10% to 20% and 80% to 90% of routine abdominopelvic CT, respectively. The MP images were reconstructed with model-based IR (MBIR) and adaptive statistical IR (ASIR). RESULTS: The MP-CT and SP-CT dose length product were 88 (58) mGy.cm (1.27 [0.87] mSv) and 303 [204] mGy.cm (4.8 [2.99] mSv), respectively (P < 0.001). Median diagnostic acceptability, spatial resolution, and contrast resolution were significantly higher and subjective noise scores were significantly lower on SP-ASIR 40 compared with all MP datasets. There was perfect clinical agreement between MP-MBIR and SP-ASIR 40 images for detection of extramural complications. CONCLUSIONS: Modified protocol CT using pure IR is feasible for assessment of active CD.

Low-Dose Carotid Computed Tomography Angiography Using Pure Iterative Reconstruction.

UNLABELLED: The aim of this study was to assess if a low-dose carotid computed tomography angiography (CTA) performed with pure iterative reconstruction (IR) is comparable to a conventional dose CTA protocol. METHODS: Twenty patients were included. Radiation dose was divided into a low-dose acquisition reconstructed with pure IR and a conventional dose acquisition reconstructed with 40% hybrid IR. Dose, image noise, contrast resolution, spatial resolution, and carotid artery stenosis were measured. RESULTS: Mean effective dose was significantly lower for low-dose than conventional dose studies (1.84 versus 3.71 mSv; P < 0.001). Subjective image noise, contrast resolution, and spatial resolution were significantly higher for the low-dose studies. There was excellent agreement for stenosis grading accuracy between low- and conventional dose studies (Cohen κ = 0.806). CONCLUSIONS: A low-dose carotid CTA protocol reconstructed with pure IR is comparable to a conventional dose CTA protocol in terms of image quality and diagnostic accuracy while enabling a dose reduction of 49.6%.

Model-Based Iterative Reconstruction in CT Enterography.

OBJECTIVE: The purpose of this study was to analyze the performance of pure model-based iterative reconstruction (MBIR) in low-dose CT enterography. SUBJECTS AND METHODS: Forty-four patients with Crohn disease referred for CT enterography were included. Low-dose modified-protocol and conventional-protocol CT datasets were contemporaneously acquired. Conventional-protocol image formation was performed with 40% adaptive statistical iterative reconstruction (ASIR). Modified-protocol data were reconstructed with 100% MBIR and 40% ASIR. Image quality was assessed subjectively and objectively at six levels. Independent clinical interpretations by two fully blinded radiologists were compared with reference standard consensus reviews by two nonblinded readers who had access to clinical information, previous imaging studies, and medical records. RESULTS: A 74.7% average radiation dose reduction was seen: low-dose modified-protocol effective dose, 1.61 ± 1.18 mSv (size-specific-dose-estimate, 2.47 ± 1.21 mGy); conventional-protocol effective dose, 6.05 ± 2.84 mSv (size-specific-dose-estimate, 9.25 ± 2.9 mGy). Image quality assessment yielded 9372 data points. Objective noise on modified-protocol MBIR images was superior (p < 0.05) to that with the conventional protocol at three of six levels and comparable at the other three levels. Modified-protocol images were superior to conventional-protocol ASIR images (p < 0.05 in all cases) for subjective noise, spatial resolution, contrast resolution, streak artifact, and diagnostic acceptability on coronal reconstructions. Axial diagnostic acceptability was superior for conventional-protocol ASIR (p = 0.76). For both readers, modified-protocol MBIR clinical readings agreed more closely with reference standard readings than did conventional-protocol ASIR readings with regard to bowel wall disease assessment (κ = 0.589 and 0.700 vs 0.583 and 0.564). Overall Crohn disease activity grade (κ = 0.549 and 0.441 vs 0.315 and 0.596) and detection of acute complications (κ = 1.0 and 0.689 vs 0.896 and 0.896) were comparable when evaluated on conventional-protocol ASIR and modified-protocol MBIR images. CONCLUSION: Low-dose CT enterography with MBIR yields images that are comparable to or superior to conventional images.

The role of pure iterative reconstruction in conventional dose CT enterography.

PURPOSE: Pure iterative reconstruction (Pure IR) has been proposed as a solution to improve diagnostic quality of low dose CT images. We assess the performance of model based iterative reconstruction (MBIR) in improving conventional dose CT enterography (CTE) images. METHODS: 43 Crohn's patients (27 female) (38.5 ± 12.98 years) referred for CTE were included. Images were reconstructed with pure IR (MBIR, General Electric Healthcare) in addition to standard department protocol (reconstructed with hybrid iterative reconstruction (Hybrid IR) [60% filtered back projection/40% adaptive statistical IR (General Electric Healthcare)]. Image quality was assessed objectively and subjectively at 6 anatomical levels. Clinical interpretation was undertaken in consensus by 2 blinded radiologists along with 2 non-blinded readers ('gold standard'). Results were analyzed using Statistical Package for Social Scientists. RESULTS: Mean effective radiation dose was 6.05 ± 2.84 mSv (size specific dose estimates 9.25 ± 2.9 mGy). Objective and subjective assessment yielded 6106 data points. Pure IR images significantly outperformed those using standard reconstruction techniques across all subjective (p < 0.001 for all comparisons) (noise, contrast resolution, spatial resolution, streak artifact, axial diagnostic acceptability, coronal diagnostic acceptability) and objective (p < 0.004) (noise, signal-to-noise ratio) parameters. Clinical reads of the pure IR images agreed more closely with the gold standard reads than the hybrid IR image reads in terms of overall Crohn's activity grade (κ = 0.630, 0.308) and detection of acute complications (κ = 1.0, 0.896). Results were comparable for bowel wall disease severity assessment (κ = 0.523, 0.593). CONCLUSIONS: Pure IR considerably improves image quality of conventional dose CTE images and therefore its use should be expanded beyond low dose protocols to improving image quality at conventional dose CT imaging.

Imaging the small bowel.

PURPOSE OF REVIEW: Radiologic investigations continue to play a pivotal role in the diagnosis of pathologic conditions of the small intestine despite enhancement of capsule endoscopy and double-balloon endoscopy. Imaging techniques continue to evolve and new techniques in MRI in particular, are being developed. RECENT FINDINGS: Continued advances in computed tomography (CT) and MRI techniques have reinforced the importance of these imaging modalities in small bowel assessment. The more invasive enteroclysis technique yields better small bowel distension for both CT and MRI when compared with peroral enterography, but no clinically significant difference is seen in terms of diagnostic accuracy. Recent concern regarding radiation exposure means that MRI is gaining in popularity. Fluoroscopic studies such as barium follow through and small bowel enteroclysis are being replaced by the cross-sectional alternatives. Contrast-enhanced ultrasound is showing results comparable with CT and MRI, but concern remains regarding reproducibility, especially outside centres that specialize in advanced sonographic techniques. SUMMARY: CT and MRI enterography are comparable first-line modalities for patients with suspected small bowel disease, but magnetic resonance enterography is favoured given the absence of ionizing radiation. Capsule endoscopy is a reasonable alternative investigation in exploration of chronic gastrointestinal blood loss, but is best kept as a second-line test in patients with other symptoms.

The utilisation and diagnostic yield of radiological imaging in a specialist functional GI disorder clinic: an 11-year retrospective study.

OBJECTIVES: The term functional gastrointestinal disorders (FGID) describes various aggregations of chronic gastrointestinal (GI) symptoms not explained by identifiable organic pathology; accordingly, their diagnosis rests on symptom-based criteria and a process of exclusion. Evidence is lacking on the appropriate use of abdominal imaging studies (AIS) in FGIDs. METHODS: We investigated the utilisation of AIS (site, modality, diagnostic yield/significance) at a tertiary FGID clinic over an 11-year period. RESULTS: Of 1,621 patients, 507 (31%; 67.5% women, mean age 43.9 ± 17.37 years) referred from primary care had 997 AIS (1.7 per patient): ultrasonography (US) 36.1%, fluoroscopy (FLS) 28.8%, computed tomography (CT) 19.6%, plain radiography (PR) 13.5%, nuclear medicine (NM) 1%). Of the 997 AIS, 55.6% (554/997) were normal. Of the AIS with positive findings, 9.9% (62/625) were deemed 'probably significant' and 14.7% (92/625) 'significant'. Of the CT and FLS studies, 12.3% and 13.6%, respectively, yielded 'significant' abnormalities compared to 2.2% of the US studies and 2.1% of the PR studies. CT identified five of seven neoplasms, associated with male sex, increasing age and symptom onset after age 50 years. CONCLUSIONS: This study confirmed low use of AIS in tertiary FGID clinics and a high proportion of normal studies. Barium swallow/meal and CT were more likely to identify 'probably significant' or 'significant' findings, including neoplasms. KEY POINTS: Imaging referral rates from a specialist functional gastrointestinal disorder clinic are low. Despite this, normal studies are still frequent in those who are imaged. Ultrasonography was the most frequent investigation, yet yielded significant findings infrequently. Abdominal radiographs accounted for 13.5% of investigations yet were normal in 71.8 %. CT and fluoroscopy were more likely to yield positive findings.

Reduction of guide needle streak artifact in CT-guided biopsy.

PURPOSE: Computed tomography (CT)-guided core needle biopsy (CNB) can be affected by streak artifact obscuring the needle tip. This study investigates factors that influence the occurrence and severity of streak artifact during CNB. MATERIALS AND METHODS: Eight coaxial guide needles of two sizes from two manufacturers with and without stylets were imaged in a CT phantom, with CT reconstructed with adaptive statistical iterative reconstruction and filtered back projection. CNB-related streak artifact was quantified with profile analysis in an image-processing program. Differences between maximum attenuation at the needle tip and minimum attenuation in the streak artifact were compared for each variable. Diagnostic acceptability and streak artifact were subjectively assessed on each phantom image and on 40 clinical CNB procedures by three independent blinded reviewers following training case review. RESULTS: Artifact was significantly less with the central stylet removed versus in situ (median, 1,145 HU vs 3,390 HU; P < .001) for all needles, and less for 19-gauge needles versus 17-gauge needles (median, 1,334 HU vs 2,780 HU, respectively; P = .006). There were no differences based on manufacturer (P = .906) or reconstruction algorithm (P = .524). Independent reviews found that streak artifact was significantly reduced when the central stylet was removed (κ = 0.875-1.0; P < .001), and needle tip position was better in cases in which the stylet was removed (κ = 0.231-0.711; P < .001). CONCLUSIONS: Streak artifact can be reduced and needle tip visualization improved by confirming final biopsy needle position with the central stylet removed on CT and using smaller-gauge guide needles.

Updated imaging nomenclature for acute pancreatitis.

Key points. 1. CT is used to confirm the diagnosis of acute pancreatitis when the diagnosis is in doubt and to differentiate acute interstitial pancreatitis from necrotizing pancreatitis, which is a key element of the updated Atlanta nomenclature. The acute interstitial variety accounts for 90-95% of cases, with acute necrotizing pancreatitis accounting for the remaining cases. 2. Necrosis due to acute pancreatitis is best assessed on IV contrast-enhanced CT performed 40 seconds after injection. Peripancreatic necrosis is a subtype of necrotizing pancreatitis in which tissue death occurs in peripancreatic tissues. This is seen in isolation in 20% of patients with necrotizing pancreatitis. 3. Simple fluid collections associated with acute interstitial pancreatitis are subdivided chronologically. A collection observed within approximately 4 weeks of acute pancreatitis onset is termed an "acute peripancreatic fluid collection (APFC)." A collection older than 4 weeks should have a thin wall and is termed a "pseudocyst." Both APFCs and pseudocysts can be infected or sterile. 4. Fluid collections associated with necrotizing pancreatitis are labeled on the basis of age and the presence of a capsule. Within 4 weeks of acute pancreatitis onset, a fluid collection associated with necrotizing pancreatitis is termed an "acute necrotic collection (ANC)" whereas an older collection is termed an area of "walled-off necrosis (WON)" if it has a perceptible wall on CT. The term "pseudocyst" is not used in the setting of necrotizing pancreatitis collections. Although an ANC and a (WON can be infected or sterile, infection is far more likely compared with acute interstitial pancreatitis collections. 5. The severity of acute pancreatitis is graded on the basis of the presence of acute complications or organ failure. Mild acute pancreatitis has neither acute complications nor organ failure. Moderate-severity acute pancreatitis is associated with acute complications or organ failure lasting fewer than 48 hours. Severe acute pancreatitis is characterized by single- or multiorgan failure persisting for greater than 48 hours.

Adult abdominal hernias.

Educational Objectives and Key Points. 1. Given that abdominal hernias are a frequent imaging finding, radiologists not only are required to interpret the appearances of abdominal hernias but also should be comfortable with identifying associated complications and postrepair findings. 2. CT is the imaging modality of choice for the assessment of a known adult abdominal hernia in both elective and acute circumstances because of rapid acquisition, capability of multiplanar reconstruction, good spatial resolution, and anatomic depiction with excellent sensitivity for most complications. 3. Ultrasound is useful for adult groin assessment and is the imaging modality of choice for pediatric abdominal wall hernia assessment, whereas MRI is beneficial when there is reasonable concern that a patient's symptoms could be attributable to a hernia or a musculoskeletal source. 4. Fluoroscopic herniography is a sensitive radiologic investigation for patients with groin pain in whom a hernia is suspected but in whom a hernia cannot be identified at physical examination. 5. The diagnosis of an internal hernia not only is a challenging clinical diagnosis but also can be difficult to diagnose with imaging: Closed-loop small-bowel obstruction and abnormally located bowel loops relative to normally located small bowel or colon should prompt assessment for an internal hernia.

Performance on the American Board of Physical Medicine and Rehabilitation certifying examinations: Rural and urban physicians.

BACKGROUND: Over 60 million people in the United States live in a rural community making up approximately 20% of the population. Data are minimal about the physiatrists who serve this rural population, their performance on certification examinations and how the American Board of Physical Medicine and Rehabilitation (ABPM&R) serves their ongoing educational, assessment, and practice needs. OBJECTIVE: To compare the performance of rural and urban physicians on the Part I, Part II, and maintenance of certification (MOC) examinations along with subspecialty preference and continuance of primary certification. DESIGN: Retrospective cross-sectional study. SETTING: Board-eligible PM&R physicians and certified diplomates of the ABPM&R. PARTICIPANTS: Physicians who participated in an initial certification or maintenance of certification examination with the ABPM&R between 2010 and 2019. METHODS: Comparisons of physician pass rates, mean scaled scores (aggregates), and program pass rates on ABPM&R certifying examinations were completed. Cross-reference to national database and ABPM&R practice site zip codes provided sociogeographic linkage. INTERVENTIONS: Not applicable MAIN OUTCOME MEASURES: Physician mean scaled scores, pass rates, subspecialty preferences, and primary certification status. RESULTS: There were no meaningful differences in performance on the ABPM&R Part I, II, and MOC examinations between rural and urban physiatrists. Most common subspecialty is the pain medicine certification whose diplomates most frequently drop their primary certification. Pediatric rehabilitation medicine certification is rare in rural localities and a health care disparity. CONCLUSION: The study found no meaningful differences in the performance of rural and urban physicians on the ABPM&R certifying examinations.

Evaluation and Treatment of the Child with Acute Back Pain.

Back pain is common, in up to 30% of children, increasing with age. Eighty percent is benign, mechanical type, improving within 2 weeks of conservative care. Required for those not improving is in-depth evaluation, including MRI, laboratory, and peer consultations. Spondylolysis and spondylolisthesis comprise almost 10% of pediatric back pain, often caused by lumbar hyperextension activities and treated conservatively in most cases. Osteoid osteomas and osteoblastomas constitute the most common benign spinal tumors in childhood. Aggressive and malignant tumors of the spine are rare but when present require tertiary care referral and a comprehensive oncology team for optimal life-sustaining outcomes.

Computational approaches for RNA energy parameter estimation.

Methods for efficient and accurate prediction of RNA structure are increasingly valuable, given the current rapid advances in understanding the diverse functions of RNA molecules in the cell. To enhance the accuracy of secondary structure predictions, we developed and refined optimization techniques for the estimation of energy parameters. We build on two previous approaches to RNA free-energy parameter estimation: (1) the Constraint Generation (CG) method, which iteratively generates constraints that enforce known structures to have energies lower than other structures for the same molecule; and (2) the Boltzmann Likelihood (BL) method, which infers a set of RNA free-energy parameters that maximize the conditional likelihood of a set of reference RNA structures. Here, we extend these approaches in two main ways: We propose (1) a max-margin extension of CG, and (2) a novel linear Gaussian Bayesian network that models feature relationships, which effectively makes use of sparse data by sharing statistical strength between parameters. We obtain significant improvements in the accuracy of RNA minimum free-energy pseudoknot-free secondary structure prediction when measured on a comprehensive set of 2518 RNA molecules with reference structures. Our parameters can be used in conjunction with software that predicts RNA secondary structures, RNA hybridization, or ensembles of structures. Our data, software, results, and parameter sets in various formats are freely available at http://www.cs.ubc.ca/labs/beta/Projects/RNA-Params.

Cerebral palsy, neurogenic bladder, and outcomes of lifetime care.

AIM: To determine the prevalence of symptomatic neurogenic bladder (SNB) and social and functional variables in a large sample of people with cerebral palsy (CP). METHOD: The medical records of 214 individuals (96 females, 118 males) with CP between the years 1990 and 2000 were retrospectively reviewed. Individuals with frequency, urgency, or incontinence were assigned Gross Motor Function Classification System levels and underwent cystometrogram/electromyelogram studies. Neurogenic bladders were classified according to the nomenclature of the International Continence Society. RESULTS: Fifty-two patients had hemiplegia, 42 diplegia, 117 quadriplegia, and three dyskinesia. Educational levels ranged from full special education to those with graduate degrees. Thirty-five individuals in our group aged 5 to 66 years had SNB with a prevalence of 16.4%. The median age for the entire population was 9 years 7 months and for those with SNB 12 years 4 months (range 5-57y). Over 80% of individuals who underwent investigation were found to have spastic hyper-reflexic type bladders. Ninety-one percent obtained total continence or major improvement with conservative care. SNB was documented across the lifespan, educational spectrum, and functional level. Upper urinary tract pathology was infrequent. INTERPRETATION: SNB is a common finding in individuals with CP. In most patients it is readily diagnosed and treated with conservative interventions.

SNVMix: predicting single nucleotide variants from next-generation sequencing of tumors.

MOTIVATION: Next-generation sequencing (NGS) has enabled whole genome and transcriptome single nucleotide variant (SNV) discovery in cancer. NGS produces millions of short sequence reads that, once aligned to a reference genome sequence, can be interpreted for the presence of SNVs. Although tools exist for SNV discovery from NGS data, none are specifically suited to work with data from tumors, where altered ploidy and tumor cellularity impact the statistical expectations of SNV discovery. RESULTS: We developed three implementations of a probabilistic Binomial mixture model, called SNVMix, designed to infer SNVs from NGS data from tumors to address this problem. The first models allelic counts as observations and infers SNVs and model parameters using an expectation maximization (EM) algorithm and is therefore capable of adjusting to deviation of allelic frequencies inherent in genomically unstable tumor genomes. The second models nucleotide and mapping qualities of the reads by probabilistically weighting the contribution of a read/nucleotide to the inference of a SNV based on the confidence we have in the base call and the read alignment. The third combines filtering out low-quality data in addition to probabilistic weighting of the qualities. We quantitatively evaluated these approaches on 16 ovarian cancer RNASeq datasets with matched genotyping arrays and a human breast cancer genome sequenced to >40x (haploid) coverage with ground truth data and show systematically that the SNVMix models outperform competing approaches. AVAILABILITY: Software and data are available at http://compbio.bccrc.ca CONTACT: sshah@bccrc.ca SUPPLEMANTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Genome-wide profiling of follicular lymphoma by array comparative genomic hybridization reveals prognostically significant DNA copy number imbalances.

The secondary genetic events associated with follicular lymphoma (FL) progression are not well defined. We applied genome-wide BAC array comparative genomic hybridization to 106 diagnostic biopsies of FL to characterize regional genomic imbalances. Using an analytical approach that defined regions of copy number change as intersections between visual annotations and a Hidden Markov model-based algorithm, we identified 71 regional alterations that were recurrent in at least 10% of cases. These ranged in size from approximately 200 kb to 44 Mb, affecting chromosomes 1, 5, 6, 7, 8, 10, 12, 17, 18, 19, and 22. We also demonstrated by cluster analysis that 46.2% of the 106 cases could be sub-grouped based on the presence of +1q, +6p/6q-, +7, or +18. Survival analysis showed that 21 of the 71 regions correlated significantly with inferior overall survival (OS). Of these 21 regions, 16 were independent predictors of OS using a multivariate Cox model that included the international prognostic index (IPI) score. Two of these 16 regions (1p36.22-p36.33 and 6q21-q24.3) were also predictors of transformation risk and independent of IPI. These prognostic features may be useful to identify high-risk patients as candidates for risk-adapted therapies.

Health Parameters in Standing and Nonstanding Nonambulatory Adults With Cerebral Palsy.

OBJECTIVE: To assess effects of standing exercise on adults with cerebral palsy with a focus on bone density, transfer skills, quality of life, and related health parameters. DESIGN: Prospective case series; pilot study. SETTING: Outpatient multispecialty clinic. PARTICIPANTS: Nonambulatory adults with cerebral palsy, 13 standers and 7 nonstanders, comparable in age, sex, and other physical characteristics (N=20). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Bone mineral density per dual energy x-ray absorptiometry, stand pivot transfers, comprehensive blood serum assessments, fractures, spasms, perceived pain, and quality of life. RESULTS: No appreciable differences could be detected between the standing and nonstanding groups from baseline and over a 2-year subsequent study with respect to bone density, range of motion, comprehensive chemistry, hematologic blood serum levels, fractures, spasms, perceived pain, continence of bowel and bladder, seizures, orthotics, and orthopedic surgery. All individuals reported positive life effects of standing with only 1 negative effect reported: increased fatigue at the end of the day. Midline independent head control >30 seconds was identified only in the standing group. Functional stand pivot transfers were seen only in individuals with a history of standing. CONCLUSIONS: The pilot data indicate no appreciable difference in measured outcome variables of a static nature between nonambulatory adults with cerebral palsy who stand compared with those who do not. We identified occurrences of improved head control and functional stand pivot transfers only in those with a history of standing. The value of a functional pivot transfer over the lifetime is difficult to overestimate. Encouragement is given toward future studies with a focus more toward functional outcome variables.

Model-based clustering of array CGH data.

MOTIVATION: Analysis of array comparative genomic hybridization (aCGH) data for recurrent DNA copy number alterations from a cohort of patients can yield distinct sets of molecular signatures or profiles. This can be due to the presence of heterogeneous cancer subtypes within a supposedly homogeneous population. RESULTS: We propose a novel statistical method for automatically detecting such subtypes or clusters. Our approach is model based: each cluster is defined in terms of a sparse profile, which contains the locations of unusually frequent alterations. The profile is represented as a hidden Markov model. Samples are assigned to clusters based on their similarity to the cluster's profile. We simultaneously infer the cluster assignments and the cluster profiles using an expectation maximization-like algorithm. We show, using a realistic simulation study, that our method is significantly more accurate than standard clustering techniques. We then apply our method to two clinical datasets. In particular, we examine previously reported aCGH data from a cohort of 106 follicular lymphoma patients, and discover clusters that are known to correspond to clinically relevant subgroups. In addition, we examine a cohort of 92 diffuse large B-cell lymphoma patients, and discover previously unreported clusters of biological interest which have inspired followup clinical research on an independent cohort. AVAILABILITY: Software and synthetic datasets are available at http://www.cs.ubc.ca/ approximately sshah/acgh as part of the CNA-HMMer package. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.