Ferumoxytol-Enhanced Magnetic Resonance Imaging in Late-Stage CKD.

Ferumoxytol is a superparamagnetic iron oxide particle encapsulated by a semisynthetic carbohydrate with properties that can be used by the nephrologist for diagnosis and therapy. Ferumoxytol is approved by the US Food and Drug Administration for treating iron deficiency anemia in the setting of chronic kidney disease, but not for clinical diagnostic imaging. It has gained appeal as a magnetic resonance imaging contrast agent in patients with estimated glomerular filtration rates < 30mL/min/1.73m(2) in whom gadolinium-based contrast magnetic resonance imaging agents are relatively contraindicated because of the association with gadolinium deposition and nephrogenic systemic fibrosis. Ferumoxytol metabolism is not dependent on kidney function, but rather is removed from the circulation by the reticuloendothelial system of the liver, spleen, and bone marrow. Additionally, the prolonged intravascular half-life (>14 hours) of ferumoxytol allows for longer image acquisition and repeat imaging, if necessary. In patients with contraindications for gadolinium contrast agents, ferumoxytol is an alternative agent for vascular assessment, including patency and course.

Periosteal Fiber Transection During Periosteal Procedures Is Crucial to Accelerate Growth in the Rabbit Model.

BACKGROUND: Disruption of the periosteum has been used to explain overgrowth after long bone fractures. Clinically, various periosteal procedures have been reported to accelerate growth with varied results. Differences between procedures and study populations, in these prior studies, make drawing conclusions regarding their effectiveness difficult. QUESTIONS/PURPOSES: The purpose of this study was to (1) determine if all reported periosteal procedures accelerate growth and increase the length of bones; (2) study the relative duration of these growth-accelerating effects at two time points; and (3) identify the periosteal procedure that results in the most growth. METHODS: Periosteal stripping (N = 8), periosteal transection (N = 8), periosteal resection (N = 8), (and) full periosteal release (N = 8) were performed on the tibiae of skeletally immature rabbits. Tibiae were collected 2 weeks postoperatively. The tibiae of additional cohorts of periosteal transection (N = 8), periosteal resection (N = 8), full periosteal release (N = 8), and repetitive periosteal transection (N = 8) were collected 8 weeks postoperatively. The contralateral tibiae served as an operative sham control in all cohorts. Fluorochrome bone labeling was used to measure growth rates, whereas high-resolution Faxitron imaging was performed to measure tibial lengths. Comparisons were then made between (1) experimental and sham controls; and (2) different procedures. Eight additional nonsurgical animals were included as age-matched controls. RESULTS: Growth (in microns) was accelerated at the proximal tibial physis on the tibia undergoing the periosteal surgical procedures versus the contralateral control limb after the transection (411 ± 27 versus 347 ± 18, p < 0.001 [mean ± SD]), resection (401 ± 33 versus 337 ± 31, p < 0.001), and full periosteal release (362 ± 45 versus 307 ± 33, p < 0.001), 2 weeks after the index procedure. Conversely, the periosteal stripping cohort trended toward less growth (344 ± 35) than the controls (356 ± 25; p = 0.08). No differences were found between limbs in the nonoperative controls. Tibial lengths for the experimental tibiae were longer at 2 weeks in the transection (1.6 ± 0.4 mm, p < 0.001), resection (1.6 ± 0.9 mm, p = 0.03), and full periosteal release (1.7 ± 0.5 mm, p < 0.001), whereas negligible differences were found between the tibiae of the nonoperative controls (0.13 ± 0.7 mm, p = 0.8) and stripping cohorts (0.10 ± 0.6 mm, p = 0.7). At 8 weeks, growth acceleration ceased at the proximal tibial physes in the transection cohort (174 ± 11 versus 176 ± 21, p = 0.8), and the control limbs actually grew faster than the experimental limbs after resection (194 ± 24 versus 178 ± 23, p = 0.02) and full periosteal release (193 ± 16 versus 175 ± 19, p < 0.01) cohorts. Growth rates were increased over control limbs, only in the repetitive transection cohort (190 ± 30 versus 169 ± 19, p = 0.01) at 8 weeks. Tibial lengths for the experimental tibiae remained longer at 8 weeks in the transection (1.4 ± 0.70 mm, p < 0.001), resection (2.2 ± 0.82 mm, p < 0.001), full periosteal release (1.6 ± 0.42 mm, p < 0.001), and repetitive periosteal transection (3.3 ± 1.1 mm, p < 0.001), whereas negligible differences were found between the tibiae of the nonoperative controls (-0.08 ± 0.58 mm, p = 0.8). Comparing the procedures at 2 weeks postoperatively, no differences were found in tibial lengths among the transection (2.1% ± 0.5% increase), resection (2.1% ± 1.1% increase), and full periosteal release (2.1% ± 0.6 %); however, all three demonstrated greater increased growth when compared with the stripping cohort (-0.10% ± 0.7%; p < 0.05). At 8 weeks no differences could be found between increased tibial lengths among the transection (1.5% ± 0.7%), resection (2.3% ± 0.9%), and full periosteal release (1.7% ± 0.4%). The repetitive transection produced the greatest over length increase (3.5% ± 1%), and this was greater than the acceleration generated by the single resection (p < 0.001) or the full periosteal release (p = 0.001). All four demonstrated an increase greater than the nonoperative control (0.09% ± 0.6%; p < 0.05). CONCLUSIONS: Transection of the longitudinally oriented periosteal fibers appears critical to accelerate growth in a rabbit model. CLINICAL RELEVANCE: These findings in an animal model support previous claims that limb overgrowth occurs as the result of periosteal disruption. Based on these findings in rabbits, we believe that less invasive procedures like periosteal transection are a promising avenue to explore in humans; clinical studies should seek to determine whether it is equally effective as more invasive procedures and its role as an adjunct to guided growth or distraction osteogenesis.

RGS4 inhibits angiotensin II signaling and macrophage localization during renal reperfusion injury independent of vasospasm.

Vascular inflammation is a major contributor to the severity of acute kidney injury. In the context of vasospasm-independent reperfusion injury we studied the potential anti-inflammatory role of the Gα-related RGS protein, RGS4. Transgenic RGS4 mice were resistant to 25 min injury, although post-ischemic renal arteriolar diameter was equal to the wild type early after injury. A 10 min unilateral injury was performed to study reperfusion without vasospasm. Eighteen hours after injury, blood flow was decreased in the inner cortex of wild-type mice with preservation of tubular architecture. Angiotensin II levels in the kidneys of wild-type and transgenic mice were elevated in a sub-vasoconstrictive range 12 and 18 h after injury. Angiotensin II stimulated pre-glomerular vascular smooth muscle cells (VSMCs) to secrete the macrophage chemoattractant RANTES, a process decreased by angiotensin II R2 (AT2) inhibition. However, RANTES increased when RGS4 expression was suppressed implicating Gα protein activation in an AT2-RGS4-dependent pathway. RGS4 function, specific to VSMC, was tested in a conditional VSMC-specific RGS4 knockout showing high macrophage density by T2 MRI compared with transgenic and non-transgenic mice after the 10 min injury. Arteriolar diameter of this knockout was unchanged at successive time points after injury. Thus, RGS4 expression, specific to renal VSMC, inhibits angiotensin II-mediated cytokine signaling and macrophage recruitment during reperfusion, distinct from vasomotor regulation.

Ossification patterns of the atlas vertebra.

OBJECTIVE: The objective of this study was to characterize ossification patterns of the C1 (atlas) vertebra in children, to better differentiate normal variants from traumatic injury. MATERIALS AND METHODS: A retrospective review of all sinus and temporal bone CT examinations was performed for the period of 2002-2009. Patients 96 months old or younger for whom C1 level was at least partially imaged were included. Patients with a history of trauma or genetic disorder-associated spinal abnormalities were excluded. RESULTS: A total of 1270 CT examinations were reviewed. The anterior arch of C1 was completely imaged in 841 patients (66%), and the posterior arch was completely imaged in 378 patients (30%). Multiple anterior arch ossification centers were observed in 179 of 841 patients (21%), and posterior arch variants were present in nine of 378 patients (2%). At least partial ossification of the anterior arch was seen in 113 of 147 children (77%) younger than 25 months, whereas only 14 of the remaining 694 children (2%) older than 24 months failed to show any ossification. Incomplete ossification of the anterior arch was noted in 47 of 103 patients (46%) in the 85-96-month-old category. The posterior arches were at least partially ossified in all children. Incomplete fusion of the posterior synchondrosis was seen in 17 of 108 patients (16%) older than 60 months. CONCLUSION: C1 ossification patterns and timing of synchondrosis fusion are variable. Knowledge of these patterns is important to better differentiate a normal variant from traumatic injury.

Use of 1.5 Tesla and 3 Tesla MRI to evaluate femoral head reduction in hip dysplasia.

BACKGROUND: To date no comparison between 1.5 Tesla (T) and 3 T magnetic resonance imaging (MRI) scans have been performed in assessing hip reduction in patients with hip dysplasia. This study compares the use of these scans in assessing hip reduction. METHODS: A retrospective review of 1.5 T and 3 T postreduction pelvic MRIs in developmental dysplasia of the hip patients for scanner time, anesthesia requirement, and subjective image quality scores were performed. Intrareader and interreader agreement of state of hip reduction was assessed. A scoring system was used to objectively compare MRI sequences between the 1.5 T and 3 T scans. RESULTS: Of the 37 MRI scans, scanner time and anesthetic requirement was not significantly different between 1.5 T and 3 T scans (P > 0.05). The 3 T scans showed slightly better image quality than 1.5 T scans (5.7 vs. 4.7), but not significant (P = 0.08). With regards to state of hip reduction, intrareader Cronbach α was 0.89 with 1.5 T and 0.98 with 3 T, whereas interreader agreement was 0.79 with 1.5 T and 0.95 with 3 T, revealing greater consistency with 3 T. Mean anatomic score comparison of hip anatomic markers show no overall statistical difference between fast hip protocol sequences (f = 1.113, sig = 0.346) or magnet strength (f = 3.817, sig = 0.053). Only the coronal T2W fast spin echo demonstrated a statistically higher score on the 3 T versus the 1.5 T (19.3 ± 9.3 vs. 12.2 ± 6.7) scanner. CONCLUSIONS: Our study affirms that adequate images are obtainable with fast hip MRI without additional anesthesia. Good agreement was reached on image quality and hip state of reduction between readers for 1.5 T and 3 T scans, with more consistency with 3 T. LEVEL OF EVIDENCE: Diagnostic Level II.

Potential Role of 3-Dimensional Printed Vascular Models in Maintenance Hemodialysis Care.

Infiltration of a surgically placed hemodialysis vascular access is recognized as a major contributor to the high health care costs associated with dialysis-dependent patients. Three-dimensional (3D) modeling is a critical tool for proceduralists in preparation for surgical interventions. No such modeling is currently available for dialysis specialists to avoid the common complication of vascular access infiltration. Ferumoxytol-enhanced magnetic resonance angiography was used to generate 3D image data that could render a 3D resin-based model of a vascular access without exposing the patient to iodinated or gadolinium-based radiologic contrast. The technique required an abbreviated magnetic resonance angiography procedure interfaced with a 3D printer workstation. An interventional radiology suite was not required. In the described case, the brachial artery was clearly delineated from a cephalic vein to basilic vein bypass with a 3D spatial resolution of 1 mm. In conclusion, we demonstrate that this new technology pathway can provide preprocedural guidance that has the potential to significantly reduce the morbidity and cost associated with vascular access infiltration.

Direct puncture of the recanalized paraumbilical vein for portal vein targeting during transjugular intrahepatic portosystemic shunt procedures: assessment of technical success and safety.

PURPOSE: To assess the success of direct percutaneous puncture of the recanalized paraumbilical vein (RPUV) for access and visualization of the portal vein (PV) to guide transhepatic puncture during transjugular intrahepatic portosystemic shunt (TIPS) creation. The predictive value of successful catheterization based on preprocedural vein diameter was analyzed. MATERIALS AND METHODS: A retrospective review of all TIPS procedures from 2002 to 2008 performed at a single institution was conducted, and a subset of procedures in which portal venography was attempted via the paraumbilical vein were identified. In this subset, TIPS outcomes and diameters of the RPUV near the skin puncture site and left PV junction were measured and analyzed with a two-tailed Student t test. RESULTS: During the study period, 114 TIPSs were created. RPUV punctures were found in 22 patients (19.3%) and portal venography was successful in 14 of the 22 patients (64%), all without complications. In the remainder (n = 8), access via the RPUV failed secondary to a small vein diameter (< 0.3 cm; n = 3), moderate to severe vessel tortuosity (n = 4), and distal thrombosis (n = 1). Puncture, catheterization, and portal venography was successful when the paraumbilical vein measured a mean of 0.75 cm at the skin and a mean of 0.84 cm at the junction with the left PV when analyzed against the failed attempts. CONCLUSIONS: Portal venography via the RPUV is a feasible and probably safe alternative to other methods of PV opacification during TIPS procedures.

Advanced quantitative imaging and biomechanical analyses of periosteal fibers in accelerated bone growth.

PURPOSE: The accepted mechanism explaining the accelerated growth following periosteal resection is that the periosteum serves as a mechanical restraint to restrict physeal growth. To test the veracity of this mechanism we first utilized Second Harmonic Generation (SHG) imaging to measure differences of periosteal fiber alignment at various strains. Additionally, we measured changes in periosteal growth factor transcription. Next we utilized SHG imaging to assess the alignment of the periosteal fibers on the bone both before and after periosteal resection. Based on the currently accepted mechanism, we hypothesized that the periosteal fibers adjacent to the physis should be more aligned (under tension) during growth and become less aligned (more relaxed) following metaphyseal periosteal resection. In addition, we measured the changes in periosteal micro- and macro-scale mechanics. METHODS: 30 seven-week old New Zealand White rabbits were sacrificed. The periosteum was imaged on the bone at five regions using SHG imaging. One centimeter periosteal resections were then performed at the proximal tibial metaphyses. The resected periosteal strips were stretched to different strains in a materials testing system (MTS), fixed, and imaged using SHG microscopy. Collagen fiber alignment at each strain was then determined computationally using CurveAlign. In addition, periosteal strips underwent biomechanical testing in both circumferential and axial directions to determine modulus, failure stress, and failure strain. Relative mRNA expression of growth factors: TGFß-1, -2, -3, Ihh, PTHrP, Gli, and Patched were measured following loading of the periosteal strips at physiological strains in a bioreactor. The periosteum adjacent to the physis of six tibiae was imaged on the bone, before and after, metaphyseal periosteal resection, and fiber alignment was computed. One-way ANOVA statistics were performed on all data. RESULTS: Imaging of the periosteum at different regions of the bone demonstrated complex regional differences in fiber orientation. Increasing periosteal strain on the resected strips increased periosteal fiber alignment (p<0.0001). The only exception to this pattern was the 10% strain on the tibial periosteum, which may indicate fiber rupture at this non-physiologic strain. Periosteal fiber alignment adjacent to the resection became less aligned while those adjacent to the physes remained relatively unchanged before and after periosteal resection. Increasing periosteal strain on the resected strips increased periosteal fiber alignment (p<0.0001). The only exception to this pattern was the 10% strain on the tibial periosteum, which may indicate fiber rupture (and consequent retraction) at this non-physiologic strain. Increasing periosteal strain revealed a significant increase in relative mRNA expression for Ihh, PTHrP, Gli, and Patched, respectively. CONCLUSION: Periosteal fibers adjacent to the growth plate do not appear under tension in the growing limb, and the alignments of these fibers remain unchanged following periosteal resection. SIGNIFICANCE: The results of this study call into question the long-accepted role of the periosteum acting as a simple mechanical tether restricting growth at the physis.