Diffusion-Weighted Imaging of the Orbit: A Case Series and Systematic Review.

PURPOSE: To describe the findings of diffusion-weighted imaging (DWI) for a series of orbital lesions and provide a systematic review of relevant literature. METHODS: A retrospective review of 20 patients with orbital lesions who underwent MRI with DWI at two academic institutions between 2015 and 2020 was performed. Lesion diagnosis was histopathologically confirmed except a presumed cavernous hemangioma. Echoplanar diffusion-weighted images had been acquired using 2 or 3 b values (b=0 and 1000 or b=0, 500, and 1000) at 1.5T or 3T. Lesions with significant artifacts were excluded. DWI sequences were analyzed by neuro-radiologists blinded to the diagnosis. Mean ADC values of lesions were calculated from a single region of interest. An independent two-tailed t test was used to compare categories of lesions with p < 0.05 considered significant. A systematic review of the literature was performed. RESULTS: Our study included 21 lesions. ADC values were significantly lower for malignant lesions (0.628 ± 0.125 × 10 -3 mm 2 /s) than inflammatory lesions (1.167 ± 0.381 × 10 -3 mm 2 /s) ( p < 0.001). ADC values were significantly lower for orbital lymphoma (mean 0.621 ± 0.147 × 10 -3 mm 2 /s) than idiopathic orbital inflammation (mean 1.188 ± 0.269 × 10 -3 mm 2 /s) with no overlap ( p < 0.001). CONCLUSIONS: Orbital malignancies demonstrated lower ADC values, while inflammatory processes demonstrated higher ADC values, except IgG4-related disease. DWI and ADC values differentiated idiopathic orbital inflammation from orbital lymphoma. This study highlights the role of DWI in evaluating orbital pathology.

All that bleeds is not black: susceptibility weighted imaging of intracranial hemorrhage and the effect of T1 signal.

PURPOSE: To determine if intracranial hemorrhages (ICH) are always hypointense on Susceptibility weighted imaging (SWI) and to determine the effect of T1-signal intensity on the appearance of ICH in SWI series. METHODS: SWI and T1-signal intensities of ICH were retrospectively studied in a series of patients. SWI signal intensities were statistically correlated with T1-signal intensities. RESULTS: In a series of 57 MRI scans from 40 patients, ICH was hypointense in 19, mixed-intensity in 21, and hyperintense in 17. Hyperintensity of ICH on SWI was significantly associated with increased T1 signal (P<.001). CONCLUSION: ICH can have a varied appearance on SWI.

Prevalence of extravertebral cement leakage after vertebroplasty: procedural documentation versus CT detection.

BACKGROUND: Reported incidence of extravertebral cement leakage after vertebroplasty varies widely across studies. PURPOSE: To retrospectively compare the relative detection rates of extravertebral leakage noted under intra-procedural fluoroscopic surveillance, postprocedure plain radiographs, and postprocedure computed tomography (CT) in a cohort of patients undergoing vertebroplasty. MATERIAL AND METHODS: With IRB approval, we retrospectively identified 181 patients with 277 levels treated with percutaneous vertebroplasty among a total of 1255 patients undergoing vertebroplasty between 1999 and 2010 who had subsequently undergone a CT examination that included the treated level(s). Categories of leakage were paravertebral, end plate, epidural, and prevertebral venous leakage. CT-detected leak rates were then compared to those noted on the vertebroplasty procedure reports and the archived fluoroscopic images for this same cohort using Pearson's χ(2) test. RESULTS: One hundred and forty-nine (82%, 95% CI 76-87%) of 181 patients demonstrated evidence of some type of leakage on CT at one or more treated levels. Sixty-two (34%, 95% CI 28-42%) and seventy-seven (50%, 95% CI 43-57%) of 149 CT-detected leaks were reported in the procedural dictation or detected on plain radiography (P = 0.01 and 0.006, respectively). The most common type of leakage noted on CT was end plate (n = 81, 45%, 95% CI 38-52%), followed by paravertebral (n = 64, 35%, 95% CI 29-43%), epidural (n = 36, 20%, 95% CI 15-26%), and prevertebral venous (n = 32, 18%, 95% CI 13-24%). CONCLUSION: Cement leakage after vertebroplasty is common and is often not reported by operators in procedural dictations. CT detects substantially more leaks than plain radiography.

Glycosaminoglycans promote fibril formation by amyloidogenic immunoglobulin light chains through a transient interaction.

Amyloid formation occurs when a precursor protein misfolds and aggregates, forming a fibril nucleus that serves as a template for fibril growth. Glycosaminoglycans are highly charged polymers known to associate with tissue amyloid deposits that have been shown to accelerate amyloidogenesis in vitro. We studied two immunoglobulin light chain variable domains from light chain amyloidosis patients with 90% sequence identity, analyzing their fibril formation kinetics and binding properties with different glycosaminoglycan molecules. We find that the less amyloidogenic of the proteins shows a weak dependence on glycosaminoglycan size and charge, while the more amyloidogenic protein responds only minimally to changes in the glycosaminoglycan. These glycosaminoglycan effects on fibril formation do not depend on a stable interaction between the two species but still show characteristic traits of an interaction-dependent mechanism. We propose that transient, predominantly electrostatic interactions between glycosaminoglycans and the precursor proteins mediate the acceleration of fibril formation in vitro.

Comparison of amyloid fibril formation by two closely related immunoglobulin light chain variable domains.

Light chain amyloidosis (AL amyloidosis) is a haematological disorder in which a clonal population of B cells expands and secretes enormous amounts of the immunoglobulin light chain protein. These light chains misfold and aggregate into amyloid fibrils, leading to organ dysfunction and death. We have studied the in vitro fibril formation kinetics of two patient-derived immunoglobulin light chain variable domain proteins, designated AL-09 and AL-103, in response to changes in solution conditions. Both proteins are members of the κI O18:O8 germline and therefore are highly similar in sequence, but they presented with different clinical phenotypes. We find that AL-09 forms fibrils more readily and more rapidly than AL-103 in vitro, mirroring the clinical phenotypes of the patients and suggesting a possible connection between the fibril kinetics of the disease protein and the disease progression.

Structural alterations within native amyloidogenic immunoglobulin light chains.

Amyloid diseases are characterized by the misfolding of a precursor protein that leads to amyloid fibril formation. Despite the fact that there are different precursors, some commonalities in the misfolding mechanism are thought to exist. In light chain amyloidosis (AL), the immunoglobulin light chain forms amyloid fibrils that deposit in the extracellular space of vital organs. AL proteins are thermodynamically destabilized compared to non-amyloidogenic proteins and some studies have linked this instability to increased fibril formation rates. Here we present the crystal structures of two highly homologous AL proteins, AL-12 and AL-103. This structural study shows that these proteins retain the canonical germ line dimer interface. We highlight important structural alterations in two loops flanking the dimer interface and correlate these results with the somatic mutations present in AL-12 and AL-103. We suggest that these alterations are informative structural features that are likely contributing to protein instability that leads to conformational changes involved in the initial events of amyloid formation.