Plasmapheresis eliminates the negative impact of AAV antibodies on microdystrophin gene expression following vascular delivery.

Duchenne muscular dystrophy is a monogenic disease potentially treatable by gene replacement. Use of recombinant adeno-associated virus (AAV) will ultimately require a vascular approach to broadly transduce muscle cells. We tested the impact of preexisting AAV antibodies on microdystrophin expression following vascular delivery to nonhuman primates. Rhesus macaques were treated by isolated limb perfusion using a fluoroscopically guided catheter. In addition to serostatus stratification, the animals were placed into one of the three immune suppression groups: no immune suppression, prednisone, and triple immune suppression (prednisone, tacrolimus, and mycophenolate mofetil). The animals were analyzed for transgene expression at 3 or 6 months. Microdystrophin expression was visualized in AAV, rhesus serotype 74 sero-negative animals (mean: 48.0 ± 20.8%) that was attenuated in sero-positive animals (19.6 ± 18.7%). Immunosuppression did not affect transgene expression. Importantly, removal of AAV binding antibodies by plasmapheresis in AAV sero-positive animals resulted in high-level transduction (60.8 ± 18.0%), which is comparable with that of AAV sero-negative animals (53.7 ± 7.6%), whereas non-pheresed sero-positive animals demonstrated significantly lower transduction levels (10.1 ± 6.0%). These data support the hypothesis that removal of AAV binding antibodies by plasmapheresis permits successful and sustained gene transfer in the presence of preexisting immunity (natural infection) to AAV.

Diagnostic and interventional ultrasound of the pediatric spine.

Ultrasound is useful as a diagnostic tool in the evaluation of the pediatric spine, and can also help guide procedures in the interventional radiology suite or the operating room. This pictorial exhibit will display examples of diagnostic and interventional uses of ultrasound with respect to the pediatric spine.

Ultrasound diagnosis of the anterior urethral valve.

We present a neonate with an obstructing anterior urethral valve depicted by longitudinal transpenile ultrasound. Voiding images are recommended to identify the obstructing valve tissue. Ultrasound depiction of the anterior urethral valve tissue is identical to that seen in posterior urethral valves.

Diagnostic and interventional ultrasonography in neonatal and infant lumbar puncture.

BACKGROUND: Lumbar puncture (LP) may be unsuccessful clinically, prompting image-guided LP by radiologists. Objective. To investigate the utility of ultrasound (US) in diagnosing the cause of failed LP and in guiding LP. MATERIALS AND METHODS: Neonates and infants referred for image-guided LP underwent spine US of the thecal sac. When indicated, image-guided LP was performed. RESULTS: Forty-seven evaluations and interventions were performed in 32 patients. All patients were initially evaluated after failed blind LP attempts. Twenty-three of the initial US studies showed intrathecal and/ or epidural echogenic hematoma, which obliterated the CSF space; 5 showed minimal fluid, and 4 had normal examinations. LP was deferred or cancelled in 14 cases based upon initial US findings. Image-guided LP was performed 32 times in 19 patients. US guidance was used in 26, fluoroscopy in 3, and fluoroscopy with US assistance in 3. Using US, LP was performed in 9 patients with no visible CSF: 2 samples were sufficient for culture only. Six patients had minimal CSF US: 4 provided usable CSF samples. Clear CSF space was seen in 11: all had successful LP. CONCLUSIONS: US can disclose the cause of failed LP, can help determine whether or not to intervene further, and can provide guidance for LP.

Percutaneous nephrostomy in children and adolescents: outpatient management.

PURPOSE: To determine if percutaneous nephrostomy can be performed safely as an outpatient procedure in children and adolescents. MATERIALS AND METHODS: Percutaneous nephrostomy was performed in 102 kidneys in 87 patients at 93 separate encounters. Patients were excluded from outpatient treatment if they presented with signs of infection, were hospitalized for other reasons, were undergoing additional endourologic stone procedures, had solitary kidneys or poor renal function, had social problems precluding outpatient care, or had a procedural complication. Follow-up was performed by means of direct communication and/or chart review. RESULTS: Successful outpatient percutaneous nephrostomy was performed in 39 (42%) of the 93 encounters. Reasons for exclusion included infection (n = 23), concomitant problems requiring hospitalization (n = 11), stone therapy (n = 7), solitary kidney with renal failure (n = 3), and social reasons (n = 10). No procedure-related complication occurred. No patient required readmission within 3 weeks for a tube- or procedure-related problem. CONCLUSION: Outpatient percutaneous nephrostomy can be safely performed in a selected group of patients.

Focused abdominal sonography for trauma (FAST) in children with blunt abdominal trauma.

BACKGROUND: Focused abdominal sonography for trauma (FAST) has been well reported in adults, but its applicability in children is less well established. We decided to test the hypothesis that FAST and computed tomography (CT) are equivalent imaging studies in the setting of pediatric blunt abdominal trauma. METHODS: One hundred seven hemodynamically stable children undergoing CT for blunt abdominal trauma were prospectively investigated using FAST. The ability of FAST to predict injury by detecting free intraperitoneal fluid was compared with CT as the imaging standard. RESULTS: Thirty-two patients had CT documented injuries. There were no late injuries missed by CT. FAST detected free fluid in 12 patients. Ten patients had solid organ injury but no free fluid and, thus, were not detected by FAST. The sensitivity of FAST relative to CT was only 0.55 and the negative predictive value was only 0.50. CONCLUSION: FAST has insufficient sensitivity and negative predictive value to be used as a screening imaging test in hemodynamically stable children with blunt abdominal trauma.

Ultrasound diagnosis of luckenschadel (lacunar skull).

BACKGROUND: The neuroradiologic findings in the Chiari II malformation are well known. Luckenschadel (lacunar skull) is commonly seen in patients with Chiari II on plain film and with computed tomography (CT). However, the sonographic appearance of luckenschadel has not previously been described. paragraph signObjective. To evaluate the presence or absence of luckenschadel on neurosonograms from infants with myelomeningocele. MATERIALS AND METHODS: Twenty-one neurosonograms in patients with myelomeningocele were reviewed for the presence of an irregular inner calvarial table indicative of luckenschadel. The degree of irregularity was graded and compared with CT and plain film when available. The ventricular index was calculated from the ultrasound (US) studies and correlated with degree of luckenschadel using one-way analysis of variance. RESULTS: Nine patients had marked findings of luckenschadel, nine had mild findings, and three had normal US exams. There was no correlation between the degree of sonographic luckenschadel and the ventricular index. CONCLUSION: The finding of luckenschadel adds to the spectrum of abnormalities of the Chiari II malformation diagnosed by US.

Importance of hypoxic/ischemic conditions in the development of cerebral lenticulostriate vasculopathy.

BACKGROUND: We have observed many infants with lenticulostriate vasculopathy (LSV) on neurosonograms who do not have classic histories of prenatal infection, trisomy, or prenatal drug exposure. OBJECTIVE: To investigate the underlying clinical conditions in patients with LSV. MATERIALS AND METHODS: Sixty-three cases of LSV were identified among approximately 2,400 neurosonograms performed over 42 months. All neurosonograms were reviewed. Medical records were reviewed for information regarding prenatal infection, chromosomal abnormality, respiratory and cardiac disease, and other pertinent diagnoses. RESULT: Hypoxic/ischemic conditions accounted for 33 cases: cardiac disease in 13, respiratory distress syndrome in 15, and perinatal asphyxia in 5. Twelve of these 33 had initially normal or minimal findings, with LSV developing or progressing on subsequent neurosonograms. The remaining 30 cases had varied clinical associations: congenital infection in 5, trisomies in 9, fetal substance exposure in 4, and unclear etiology in 12. Coexistent anomalies included posterior urethral valves, MCDK, myelomeningocele, placental abruption, and others. Thirty patients were premature. Fifteen patients died; histologic changes of LSV were found at autopsy in one patient. CONCLUSION: LSV has varied clinical associations. The common association with hypoxic/ischemic conditions and the progressive changes seen in 12 patients with cardiac and pulmonary disease suggest that postnatal hypoxia/ischemia is an important etiologic factor.

Preliminary experience with focused abdominal sonography for trauma (FAST) in children: is it useful?

BACKGROUND/PURPOSE: Most pediatric surgeons and pediatric radiologists consider computed tomography (CT) the best radiological test for the evaluation of children with suspected intraabdominal injury. The majority of injured children evaluated with CT will be found to have a normal scan. Focused abdominal sonography for trauma (FAST) has been shown to be a useful screening test in the evaluation of adult patients with suspected intraabdominal injury. Limited data exist regarding the use of FAST in children. Our aim was to evaluate the usefulness of FAST as a screening test in the evaluation of children with suspected intraabdominal injury in an attempt to minimize the number of normal CT scans performed. METHODS: Hemodynamically stable children evaluated for suspected intraabdominal injury were prospectively screened with FAST. FAST, real-time sonography at four sites, was performed by staff pediatric radiologists. The average duration of the examination was 2 minutes. Positive and negative FAST scan findings were defined prospectively. The result of each FAST was recorded (positive or negative) and then all patients underwent CT as a control. All management decisions were based on CT results. RESULTS: Forty-six patients were included in the study. FAST identified four children with positive findings (free intraperitoneal fluid), whereas CT showed 13 children with injuries (nine with associated free intraperitoneal fluid and four with only solid organ injury and no associated intraperitoneal fluid). There were nine false-negative and no false-positive FAST scans. The sensitivity of FAST was 0.3 and the specificity was 1.0. Injuries missed by FAST included liver laceration, adrenal hematoma, renal laceration, small bowel injury and splenic laceration. CONCLUSION: Preliminary results suggest that FAST alone is not a useful screening test in the evaluation of children with suspected intraabdominal injury.

Sonographic findings in splenogonadal fusion.

Splenogonadal fusion is a rare developmental anomaly usually presenting as a scrotal mass. The imaging findings and etiology of this condition are discussed. Knowledge of this entity may help to prevent unnecessary orchiectomy.

Radiological pulmonary changes during gram-negative bacillary nosocomial bloodstream infection in premature infants.

OBJECTIVE: The objective of the study was to characterize the changes that occur in chest radiographs at the time of gram-negative bacilli (GNB) nosocomial bloodstream infection (BSI) and to determine the contribution of bronchopulmonary dysplasia (BPD) and airway gram-negative bacterial pathogens to the clinical diagnosis of GNB nosocomial pneumonia. STUDY DESIGN: This retrospective investigation involved 41 BSI infants (study group) and 50 GNB airway colonized infants who had sepsis workup with negative blood cultures (control group). We correlated clinical findings (95 blood and 305 tracheal aspirate (TA) cultures) with radiographic findings noted within 2 days before, the day of, and the day after blood cultures. Two radiologists independently graded 258 films using a modified score for BPD and a semiquantitative score ("probable," "possible," or "unlikely") for pneumonia. RESULTS: Mean birth weight was 1057 gm and 1044 gm for the study and control groups, respectively. Of the study population, 54% were male, 21% were black, 89% received surfactant, 79% received dexamethasone, and 88% survived. Average age at the time of blood cultures for both groups was 23 days. Most common isolates from blood and TA were Klebsiella pneumoniae, Enterobacter cloacae, Escherichia coli, and Pseudomonas aeruginosa. Eight BSI infants died, mainly as a result of P. aeruginosa and K. pneumoniae; three control patients also died. Radiological findings were that BPD scores did not change in relation to BSI and were similar between study and control groups. Of the BSI patients, 21 presented with newly positive TA at the time of positive blood culture; "probable" or "possible" pneumonia was diagnosed in 18 of them. Their BPD scores were higher than those of the remaining BSI patients, of whom seven were already airway colonized, nine had negative TAs, and four were not intubated. Only one of these 20 patients had "possible" pneumonia noted on chest x-ray films. CONCLUSION: Radiographic signs of air space disease accompanied by the recovery of GNB respiratory pathogens from the blood and from a previously uncolonized airway strongly support the clinical diagnosis of GNB nosocomial pneumonia. Radiological signs of BPD are stable in relation to nosocomial BSI caused by GNB, but BPD radiological scores are higher among infants who also had a newly acquired respiratory GNB. BSI, new respiratory tract GNB, and BPD are critical associations for the clinical interpretation of radiographic changes in the ventilated newborn.

Recurrent deep venous thrombosis complicating PICC line placement in two patients with cystic fibrosis and activated protein C-resistance.

Two patients with cystic fibrosis and activated protein C-resistance experienced deep vein thrombosis complicating peripherally inserted central catheter (PICC) use. Cystic fibrosis patients may be at increased risk for catheter rotated thrombosis.

Preamputation MR imaging in meningococcemia and comparison to conventional arteriography.

Meningococcemia is a life-threatening infection which produces purpura fulminans and extremity gangrene in its most severe form. In patients with gangrene, amputation is usually necessary. The amputations frequently need revision as ischemic changes in the underlying soft tissues and bone are difficult to evaluate at the time of surgery. These ischemic changes often have non-vascular distributions and progress over time. We present two patients in whom MR imaging and MR angiography were performed prior to planned amputation. These cases demonstrate the potential utility of MR imaging in this setting, and compare the MR angiographic results to conventional arteriography in one of these patients.

Neonatal total parenteral nutrition ascites from liver erosion by umbilical vein catheters.

BACKGROUND: A preterm infant was found to have total parenteral nutrition (TPN) ascites after infusion through a low umbilical vein catheter (UVC). Objective. To evaluate the clinical and imaging findings of neonates with TPN ascites after infusion through UVCs. MATERIALS AND METHODS: Eight patients with TPN ascites were identified over three years. Charts were abstracted for clinical data. Plain-film, ultrasound (US), and contrast studies through the UVCs were examined to determine UVC placement, presence of liver injury, and confirmation of intraperitoneal extravasation from the UVC. RESULTS: All eight patients with TPN ascites presented with hypotension and abdominal distension. All had UVCs overlying the liver on plain film. Catheters were in place a mean of 8.9 days prior to TPN extravasation. US in four patients showed hepatic parenchymal damage around the UVC tip. Contrast studies in six patients showed intraperitoneal spill. CONCLUSION: While low UVC placement may sometimes be clinically unavoidable, TPN administered through abnormally positioned UVCs is not without risk.

Cystic periventricular leukomalacia of the corpus callosum.

Periventricular leukomalacia (PVL) is a common finding during neurosonography of preterm infants. Secondary thinning of the corpus callosum is seen following PVL, typically from loss of hemispheric white matter tracts. We report a case of direct involvement of the corpus callosum with PVL, its pathogenesis, and its potential as a cause of corpus callosal thinning.

Bacterial and Ureaplasma colonization of the airway: radiologic findings in infants with bronchopulmonary dysplasia.

OBJECTIVE: We designed this retrospective study to compare radiologic findings in premature infants with bronchopulmonary dysplasia (BPD) in whom gram-positive cocci (GPC), gram-negative bacilli (GNB), or Ureaplasma urealyticum were colonized. Another objective was to correlate the radiologic findings of these patients with the clinical severity of BPD. STUDY DESIGN: We correlated serial tracheal aspirates with radiographic findings from 183 infants whose birth weight was < or = 1250 gm. BPD severity was assessed by oxygen dependency at 36 weeks of postconceptional age (36 w PCA) and at the time of discharge. Two radiologists independently scored films taken at birth and 1, 7, 14, 21, 28, and 35 days of life. RESULTS: Of the study population, 55% were male and 35% were black; 80% received surfactant and 69% received dexamethasone; 91% survived. GPC isolates from throat cultures were mainly Staphylococcus [corrected] epidermidis and Streptococcus haemolyticus. A superimposed GNB colonization was present in 37% of these infants. Most common isolates were Klebsiella pneumoniae, Enterobacter cloacae, and Escherichia coli. Sepsis caused by GPC developed in 16% of all patients; 7% had sepsis caused by GNB. Infants infected with GNB remained receiving oxygen at 36 w PCA and at the time of discharge twice as often as those noninfected. RADIOLOGIC FINDINGS: Hyperinflation, interstitial changes, and generalized or localized emphysema were prominent features throughout. Mean radiologic scores increased over time in a pattern similar among GPC, GNB, and U. urealyticum infected and noninfected infants. High radiologic scores were not predictive at any time of infants who needed supplemental oxygen at 28 days and at 36 w PCA. Infants infected with U. urealyticum were neither clinically nor radiologically different than noncolonized neonates. CONCLUSION: GPC, GNB, and U. urealyticum airway colonization is not associated with particular radiographic changes at any time. GNB-infected infants had the most severe BPD course, and yet they were radiologically indistinguishable from the other patients. U. urealyticum colonization does not result in more clinically severe BPD or demonstrate a unique radiologic course.

Acute testicular torsion: comparison of unenhanced and contrast-enhanced power Doppler US, color Doppler US, and radionuclide imaging.

PURPOSE: To compare the usefulness of conventional color Doppler ultrasound (US), unenhanced and contrast material-enhanced power Doppler US, and radionuclide imaging in a model of acute testicular torsion. MATERIALS AND METHODS: Twenty rabbits underwent unilateral 360 degree testis torsion and contralateral orchiopexy. Gray-scale, color Doppler, and unenhanced and contrast-enhanced power Doppler US were performed 4-6 hours later. The side of torsion was determined, and intratestis flow was graded. Within 2 hours of US, technetium-99m pertechnetate was intravenously administered, the rabbits were killed, and the testes excised for radionuclide imaging. RESULTS: Intratestis perfusion was detected in 85% of torsed testes at US and radionuclide imaging. The side of torsion was correctly diagnosed in 25% of cases with radionuclide imaging and in 60% of cases with US. Power Doppler US demonstrated significantly greater intratestis flow in pexed than in torsed testes. Although the numbers of correct diagnosis with the three US modalities were similar, flow grades within torsed and normal testes were significantly different. CONCLUSION: Perfusion to torsed and normal testes was demonstrated equally well with color Doppler US, power Doppler US, and radionuclide imaging. Doppler US better depicted differences in intratesticular flow between torsed and normal testes.

Renal resistive index in experimental partial and complete ureteral obstruction.

RATIONALE AND OBJECTIVES: Recent clinical work suggests that the Doppler resistive index (RI) may be useful in distinguishing obstructive from nonobstructive hydronephrosis. We evaluated the usefulness of the RI in a rabbit model of hydronephrosis. METHODS: Unilateral partial ureteral obstruction was produced in nine rabbits and complete obstruction in another nine. Three sham operations were performed, and these animals served as control subjects. The RI was measured in all kidneys before and 6 hr after surgery and on days 1, 4, and 7 postoperatively. The RI and the difference in RI (delta RI) between the obstructed and normal kidney were evaluated over time using a two-way analysis of variance. The intravenous urography and Whitaker tests served as gold standards. RESULTS: Hydronephrosis was observed on sonograms in all obstructed kidneys. Comparing groups, there was no significant difference in mean RI or delta RI between the three groups at any time point. Looking at individual groups over time, there was no significant change in mean delta RI, whereas the change in mean RI was significantly elevated above baseline only in the complete obstruction group at 6 hr (p = .002) and on days 4 (p = .008) and 7 (p = .006). In evaluating varying thresholds of RI and delta RI, we could not consistently discriminate between normal and obstructed kidneys. CONCLUSION: Although complete obstruction caused a significant increase in RI, partial obstruction failed to do so. RI and delta RI values proved to be insensitive predictors of obstruction in this rabbit model.