Fetal neuroimaging applications for diagnosis and counseling of brain anomalies: Current practice and future diagnostic strategies.

Advances in fetal brain neuroimaging, especially fetal neurosonography and brain magnetic resonance imaging (MRI), allow safe and accurate anatomical assessments of fetal brain structures that serve as a foundation for prenatal diagnosis and counseling regarding fetal brain anomalies. Fetal neurosonography strategically assesses fetal brain anomalies suspected by screening ultrasound. Fetal brain MRI has unique technological features that overcome the anatomical limits of smaller fetal brain size and the unpredictable variable of intrauterine motion artifact. Recent studies of fetal brain MRI provide evidence of improved diagnostic and prognostic accuracy, beginning with prenatal diagnosis. Despite technological advances over the last several decades, the combined use of different qualitative structural biomarkers has limitations in providing an accurate prognosis. Quantitative analyses of fetal brain MRIs offer measurable imaging biomarkers that will more accurately associate with clinical outcomes. First-trimester ultrasound opens new opportunities for risk assessment and fetal brain anomaly diagnosis at the earliest time in pregnancy. This review includes a case vignette to illustrate how fetal brain MRI results interpreted by the fetal neurologist can improve diagnostic perspectives. The strength and limitations of conventional ultrasound and fetal brain MRI will be compared with recent research advances in quantitative methods to better correlate fetal neuroimaging biomarkers of neuropathology to predict functional childhood deficits. Discussion of these fetal sonogram and brain MRI advances will highlight the need for further interdisciplinary collaboration using complementary skills to continue improving clinical decision-making following precision medicine principles.

Segmenting hypothalamic subunits in human newborn magnetic resonance imaging data.

Preclinical evidence suggests that inter-individual variation in the structure of the hypothalamus at birth is associated with variation in the intrauterine environment, with downstream implications for future disease susceptibility. However, scientific advancement in humans is limited by a lack of validated methods for the automatic segmentation of the newborn hypothalamus. N = 215 healthy full-term infants with paired T1-/T2-weighted MR images across four sites were considered for primary analyses (mean postmenstrual age = 44.3 ± 3.5 weeks, nmale /nfemale = 110/106). The outputs of FreeSurfer's hypothalamic subunit segmentation tools designed for adults (segFS) were compared against those of a novel registration-based pipeline developed here (segATLAS) and against manually edited segmentations (segMAN) as reference. Comparisons were made using Dice Similarity Coefficients (DSCs) and through expected associations with postmenstrual age at scan. In addition, we aimed to demonstrate the validity of the segATLAS pipeline by testing for the stability of inter-individual variation in hypothalamic volume across the first year of life (n = 41 longitudinal datasets available). SegFS and segATLAS segmentations demonstrated a wide spread in agreement (mean DSC = 0.65 ± 0.14 SD; range = {0.03-0.80}). SegATLAS volumes were more highly correlated with postmenstrual age at scan than segFS volumes (n = 215 infants; RsegATLAS 2 = 65% vs. RsegFS 2 = 40%), and segATLAS volumes demonstrated a higher degree of agreement with segMAN reference segmentations at the whole hypothalamus (segATLAS DSC = 0.89 ± 0.06 SD; segFS DSC = 0.68 ± 0.14 SD) and subunit levels (segATLAS DSC = 0.80 ± 0.16 SD; segFS DSC = 0.40 ± 0.26 SD). In addition, segATLAS (but not segFS) volumes demonstrated stability from near birth to ~1 years age (n = 41; R2 = 25%; p < 10-3 ). These findings highlight segATLAS as a valid and publicly available (https://github.com/jerodras/neonate_hypothalamus_seg) pipeline for the segmentation of hypothalamic subunits using human newborn MRI up to 3 months of age collected at resolutions on the order of 1 mm isotropic. Because the hypothalamus is traditionally understudied due to a lack of high-quality segmentation tools during the early life period, and because the hypothalamus is of high biological relevance to human growth and development, this tool may stimulate developmental and clinical research by providing new insight into the unique role of the hypothalamus and its subunits in shaping trajectories of early life health and disease.

Biometric magnetic resonance imaging analysis of fetal brain development in Down syndrome.

OBJECTIVES: To assess brain development in living fetuses with Down syndrome (DS) by biometric measurements on fetal brain magnetic resonance images (MRI). METHODS: We scanned 10 MRIs of fetuses with confirmed trisomy 21 at birth and 12 control fetal MRIs without any detected anomalies. Fetal brain MRIs were analyzed using 14 fetal brain and skull biometric parameters. We compared measures between DS and controls in both raw MRIs and motion-corrected and anterior-posterior commissure-aligned images. RESULTS: In the reconstructed images, the measured values of the height of the cerebellar vermis (HV) and anteroposterior diameter of the cerebellar vermis (APDV) were significantly smaller, and the anteroposterior diameter of the fourth ventricle (APDF) was significantly larger in fetuses with DS than controls. In the raw MRIs, the measured values of the right lateral ventricle were significantly larger in fetuses with DS than in controls. Logistic regression analyses revealed that a new parameter, the cerebellar-to-fourth-ventricle ratio (i.e., (APDV * Height of the vermis)/APDF), was significantly smaller in fetuses with DS than controls and was the most predictive to distinguish between fetuses with DS and controls. CONCLUSIONS: The study revealed that fetuses with DS have smaller cerebellums and larger fourth ventricles compared to the controls.

Comprehensive quantitative analyses of fetal magnetic resonance imaging in isolated cerebral ventriculomegaly.

Isolated cerebral ventriculomegaly (IVM) is the most common prenatally diagnosed brain anomaly occurs in 0.2-1 % of pregnancies. However, knowledge of fetal brain development in IVM is limited. There is no prenatal predictor for IVM to estimate individual risk of neurodevelopmental disability occurs in 10 % of children. To characterize brain development in fetuses with IVM and delineate their individual neuroanatomical variances, we performed comprehensive post-acquisition quantitative analysis of fetal magnetic resonance imaging (MRI). In volumetric analysis, brain MRI of fetuses with IVM (n = 20, 27.0 ± 4.6 weeks of gestation, mean ± SD) had revealed significantly increased volume in the whole brain, cortical plate, subcortical parenchyma, and cerebrum compared to the typically developing fetuses (controls, n = 28, 26.3 ± 5.0). In the cerebral sulcal developmental pattern analysis, fetuses with IVM had altered sulcal positional (both hemispheres) development and combined features of sulcal positional, depth, basin area, in both hemispheres compared to the controls. When comparing distribution of similarity index of individual fetuses, IVM group had shifted toward to lower values compared to the control. About 30 % of fetuses with IVM had no overlap with the distribution of control fetuses. This proof-of-concept study shows that quantitative analysis of fetal MRI can detect emerging subtle neuroanatomical abnormalities in fetuses with IVM and their individual variations.

Sex-specific inflammatory and white matter effects of prenatal opioid exposure: a pilot study.

BACKGROUND: Preclinical data demonstrate that opioids modulate brain reward signaling through an inflammatory cascade, but this relationship has yet to be studied in opioid-exposed neonates. METHODS: Saliva samples of 54 opioid-exposed and sex- and age-matched non-exposed neonates underwent transcriptomic analysis of inflammatory and reward genes. A subset of 22 neonates underwent brain magnetic resonance imaging (MRI) to evaluate white matter injury commonly associated with inflammatory response. Gene expression and brain MRI were compared between opioid- and non-exposed neonates and further stratified by sex and pharmacotherapy need. RESULTS: Opioid-exposed females regardless of pharmacotherapy need had higher expression of inflammatory genes than their male counterparts, with notable differences in the expression of CCL2 and CXCL1 in females requiring pharmacotherapy (p = 0.01 and 0.06, respectively). Opioid-exposed males requiring pharmacotherapy had higher expression of DRD2 than exposed females (p = 0.07), validating our prior research. Higher expression of IL1ß, IL6, TNFα, and IL10 was seen in opioid-exposed neonates with T1 white matter hyperintensity (WMH) compared to exposed neonates without WMH (p < 0.05). CONCLUSION: Prenatal opioid exposure may promote inflammation resulting in changes in reward signaling and white matter injury in the developing brain, with unique sex-specific effects. The actions of opioids through non-neuronal pathways need further investigation. IMPACT: Opioid-exposed neonates are at risk for punctate T1 white matter hyperintensity (WMH). Females carry a greater propensity for WMH. Salivary transcriptomic data showed significantly higher expression of inflammatory genes in opioid-exposed neonates with WMH than those without WMH, irrespective of pharmacotherapy need. Adding to prior studies, our findings suggest that prenatal opioid exposure may modulate white matter injury and reward signaling through a pro-inflammatory process that is sex specific. This novel study highlights the short-term molecular and structural effects of prenatal opioids and the need to elucidate the long-term impact of prenatal opioid exposure.

Cavernous segment internal carotid artery stenosis specific to meningiomas compared to pituitary adenomas.

BACKGROUND AND PURPOSE: Pituitary macroadenomas and meningiomas are common neoplasms arising within the cavernous sinus. Imaging characteristics on MRI can often distinguish these tumors from one another; however, some cases may be more difficult to differentiate. This study compares patterns of cavernous segment internal carotid artery (CS-ICA) stenosis between the two tumor types to establish a novel radiographic method of differentiation. METHODS: A retrospective analysis of patients with pathology-confirmed meningioma and pituitary adenomas at Tufts Medical Center was performed. The diameter of the CS-ICA at the narrowest point within the cavernous sinus was measured and compared to the ipsilateral petrous segment ICA and contralateral CS-ICA. The mean and range of percent stenosis and frequency of cases of CS-ICA stenosis >15% were determined. Statistical analysis to compare the groups was conducted using the Chi-squared test, Fisher's exact test, and t-test. RESULTS: There were a total of 78 out of 231 patients who were included in the study. The mean % ICA stenosis for all meningiomas was 9.3%, with increasing stenosis with increasing World Health Organization grade. Of all meningioma cases, 13 (33%) had greater than 15% ICA stenosis. Mean ICA stenosis for pituitary adenomas was -1.48%. There were no cases of pituitary adenomas causing ICA stenosis >15%. CONCLUSIONS: Differentiating pituitary adenomas and intracavernous meningioma tumors can have important implications on surgical approach and outcome. Our study found that stenosis of the CS-ICA greater than 15% is highly specific to meningiomas and can serve as a radiologic sign to distinguish between these two tumors.

Regional brain development in fetuses with Dandy-Walker malformation: A volumetric fetal brain magnetic resonance imaging study.

Dandy-Walker malformation (DWM) is a common prenatally diagnosed cerebellar malformation, characterized by cystic dilatation of the fourth ventricle, upward rotation of the hypoplastic vermis, and posterior fossa enlargement with torcular elevation. DWM is associated with a broad spectrum of neurodevelopmental abnormalities such as cognitive, motor, and behavioral impairments, which cannot be explained solely by cerebellar malformations. Notably, the pathogenesis of these symptoms remains poorly understood. This study investigated whether fetal structural developmental abnormalities in DWM extended beyond the posterior fossa to the cerebrum even in fetuses without apparent cerebral anomalies. Post-acquisition volumetric fetal magnetic resonance imaging (MRI) analysis was performed in 12 fetuses with DWM and 14 control fetuses. Growth trajectories of the volumes of the cortical plate, subcortical parenchyma, cerebellar hemispheres, and vermis between 18 and 33 weeks of gestation were compared. The median (interquartile range) gestational ages at the time of MRI were 22.4 (19.4-24.0) and 23.9 (20.6-29.2) weeks in the DWM and control groups, respectively (p = 0.269). Eight of the 12 fetuses with DWM presented with associated cerebral anomalies, including hydrocephalus (n = 3), cerebral ventriculomegaly (n = 3), and complete (n = 2) and partial (n = 2) agenesis of the corpus callosum (ACC); 7 presented with extracerebral abnormalities. Chromosomal abnormalities were detected by microarray analysis in 4 of 11 fetuses with DWM, using amniocentesis. Volumetric analysis revealed that the cortical plate was significantly larger in fetuses with DWM than in controls (p = 0.040). Even without ACC, the subcortical parenchyma, whole cerebrum, cerebellar hemispheres, and whole brain were significantly larger in fetuses with DWM (n = 8) than in controls (p = 0.004, 0.025, 0.033, and 0.026, respectively). In conclusion, volumetric fetal MRI analysis demonstrated that the development of DWM extends throughout the brain during the fetal period, even without apparent cerebral anomalies.

Agreement between neuroimages and reports for natural language processing-based detection of silent brain infarcts and white matter disease.

BACKGROUND: There are numerous barriers to identifying patients with silent brain infarcts (SBIs) and white matter disease (WMD) in routine clinical care. A natural language processing (NLP) algorithm may identify patients from neuroimaging reports, but it is unclear if these reports contain reliable information on these findings. METHODS: Four radiology residents reviewed 1000 neuroimaging reports (RI) of patients age > 50 years without clinical histories of stroke, TIA, or dementia for the presence, acuity, and location of SBIs, and the presence and severity of WMD. Four neuroradiologists directly reviewed a subsample of 182 images (DR). An NLP algorithm was developed to identify findings in reports. We assessed interrater reliability for DR and RI, and agreement between these two and with NLP. RESULTS: For DR, interrater reliability was moderate for the presence of SBIs (k = 0.58, 95 % CI 0.46-0.69) and WMD (k = 0.49, 95 % CI 0.35-0.63), and moderate to substantial for characteristics of SBI and WMD. Agreement between DR and RI was substantial for the presence of SBIs and WMD, and fair to substantial for characteristics of SBIs and WMD. Agreement between NLP and DR was substantial for the presence of SBIs (k = 0.64, 95 % CI 0.53-0.76) and moderate (k = 0.52, 95 % CI 0.39-0.65) for the presence of WMD. CONCLUSIONS: Neuroimaging reports in routine care capture the presence of SBIs and WMD. An NLP can identify these findings (comparable to direct imaging review) and can likely be used for cohort identification.

Automated Detection of COVID-19 Cases on Radiographs using Shape-Dependent Fibonacci-p Patterns.

The coronavirus (COVID-19) pandemic has been adversely affecting people's health globally. To diminish the effect of this widespread pandemic, it is essential to detect COVID-19 cases as quickly as possible. Chest radiographs are less expensive and are a widely available imaging modality for detecting chest pathology compared with CT images. They play a vital role in early prediction and developing treatment plans for suspected or confirmed COVID-19 chest infection patients. In this paper, a novel shape-dependent Fibonacci-p patterns-based feature descriptor using a machine learning approach is proposed. Computer simulations show that the presented system (1) increases the effectiveness of differentiating COVID-19, viral pneumonia, and normal conditions, (2) is effective on small datasets, and (3) has faster inference time compared to deep learning methods with comparable performance. Computer simulations are performed on two publicly available datasets; (a) the Kaggle dataset, and (b) the COVIDGR dataset. To assess the performance of the presented system, various evaluation parameters, such as accuracy, recall, specificity, precision, and f1-score are used. Nearly 100% differentiation between normal and COVID-19 radiographs is observed for the three-class classification scheme using the lung area-specific Kaggle radiographs. While Recall of 72.65 ± 6.83 and specificity of 77.72 ± 8.06 is observed for the COVIDGR dataset.

Primary meningeal melanoma masquerading as neurofibromatosis type 2: illustrative case.

BACKGROUND: Primary meningeal melanocytic neoplasms are exceedingly rare tumors, representing only 0.06% to 0.1% of all primary brain tumors and ranging in spectrum from benign localized tumors to highly aggressive malignant lesions. The diagnosis of these tumors is often challenging from clinical, radiological, and pathologic standpoints. Equally challenging is the distinction between primary meningeal melanocytic neoplasm and metastatic melanoma. OBSERVATIONS: The authors reported the case of a 41-year-old man with imaging findings diagnostic of neurofibromatosis type 2: bilateral internal auditory canal lesions (most consistent with bilateral vestibular schwannomas), two dura-based lesions presumed to be meningiomas, multiple spinal lesions consistent with peripheral nerve sheath tumors, and one intramedullary spinal lesion consistent with an ependymoma. Biopsy of these lesions revealed melanocytic neoplasms with mild to moderate atypia and a mildly elevated proliferation index, which made the distinction between benign and malignant challenging. In addition, the disseminated nature of these tumors made it difficult to determinate whether they arose from the meninges or represented metastases from an occult primary melanoma. LESSONS: This case illustrated the challenges presented by the diagnosis of meningeal melanocytic neoplasms and highlighted the importance of integrating the clinical and radiographic findings with histologic appearance and molecular studies.

Regional Alterations in Cortical Sulcal Depth in Living Fetuses with Down Syndrome.

Down syndrome (DS) is the most common genetic cause of developmental disabilities. Advanced analysis of brain magnetic resonance imaging (MRI) has been used to find brain abnormalities and their relationship to neurocognitive impairments in children and adolescents with DS. Because genetic factors affect brain development in early fetal life, there is a growing interest in analyzing brains from living fetuses with DS. In this study, we investigated regional sulcal folding depth as well as global cortical gyrification from fetal brain MRIs. Nine fetuses with DS (29.1 ± 4.24 gestational weeks [mean ± standard deviation]) were compared with 17 typically developing [TD] fetuses (28.4 ± 3.44). Fetuses with DS showed lower whole-brain average sulcal depths and gyrification index than TD fetuses. Significant decreases in sulcal depth were found in bilateral Sylvian fissures and right central and parieto-occipital sulci. On the other hand, significantly increased sulcal depth was shown in the left superior temporal sulcus, which is related to atypical hemispheric asymmetry of cortical folding. Moreover, these group differences increased as gestation progressed. This study demonstrates that regional sulcal depth is a sensitive marker for detecting alterations of cortical development in DS during fetal life, which may be associated with later neurocognitive impairment.

Rapid Cognitive Decline Secondary to CSF Venous Fistula With Postoperative Rebound Intracranial Hypertension and a Hyperintense Paraspinal Vein Sign Seen Retrospectively.

A 56-year-old female with 2 prior Chiari decompressions presented with rapidly progressive cognitive decline. Brain magnetic resonance imaging, computed tomography myelogram, and prone digital subtraction myelography revealed signs of brain sag and left T9 perineural cysts but no cerebrospinal fluid leaks. Symptoms improved after multilevel blood patches but recurred. Lateral decubitus digital subtraction myelography revealed a spinal cerebrospinal fluid venous fistula (SCVF), which resolved after neurosurgeons ligated the nerve root. Rebound headaches with papilledema occurred on postoperative day 9 and then resolved 2 months after acetazolamide was started. A hyperintense paraspinal vein was seen retrospectively on T2-weighted magnetic resonance imaging with Dixon fat suppression sequencing. This case is unique in the acuity of cognitive decline secondary to SCVF. Acetazolamide at the time of treatment may potentially be used as prophylaxis for rebound intracranial hypertension. The hyperintense paraspinal vein may have utility in future diagnosis of SCVF.

Quantitative MRI Analyses of Regional Brain Growth in Living Fetuses with Down Syndrome.

Down syndrome (DS) is the most common liveborn autosomal chromosomal anomaly and is a major cause of developmental disability. Atypical brain development and the resulting intellectual disability originate during the fetal period. Perinatal interventions to correct such aberrant development are on the horizon in preclinical studies. However, we lack tools to sensitively measure aberrant structural brain development in living human fetuses with DS. In this study, we aimed to develop safe and precise neuroimaging measures to monitor fetal brain development in DS. We measured growth patterns of regional brain structures in 10 fetal brains with DS (29.1 ± 4.2, weeks of gestation, mean ± SD, range 21.7~35.1) and 12 control fetuses (25.2 ± 5.0, range 18.6~33.3) using regional volumetric analysis of fetal brain MRI. All cases with DS had confirmed karyotypes. We performed non-linear regression models to compare fitted regional growth curves between DS and controls. We found decreased growth trajectories of the cortical plate (P = 0.033), the subcortical parenchyma (P = 0.010), and the cerebellar hemispheres (P < 0.0001) in DS compared to controls. This study provides proof of principle that regional volumetric analysis of fetal brain MRI facilitates successful evaluation of brain development in living fetuses with DS.

Spinal subarachnoid space tapering in patients with syringomyelia.

BACKGROUND AND PURPOSE: Cervical spine tapering affects cerebrospinal fluid dynamics. Cervical spine taper ratios derived from anteroposterior diameters reportedly differ between patients with syringomyelia and controls. We attempted to verify the differences in diameter and to show differences in cross-sectional area between syringomyelia and controls. METHODS: Cervical spine magnetic resonance images in syringomyelia patients (idiopathic or Chiari I related) and control patients were examined. In each subject, the anteroposterior diameter of the spinal canal was measured at each cervical level, and C1-C4, C4-C7, and C1-C7 taper ratios were calculated. Differences in taper ratio between groups were tested for statistical significance with the t-test. Cross-sectional areas of the spinal canal were measured at each cervical spinal level, and tapering was calculated. RESULTS: Eighteen patients with idiopathic syringomyelia, 28 with Chiari I, and 29 controls were studied. Chiari and syringomyelia patients had significantly steeper diameter-based taper ratios than controls. The dural sac areas tapered proportionally with the diameter-based taper ratio in all groups. CONCLUSIONS: Cervical spine anteroposterior diameter tapering and dural sac cross-sectional areas tapering differ between syringomyelia patients and controls.

Disorganized Patterns of Sulcal Position in Fetal Brains with Agenesis of Corpus Callosum.

Fetuses with isolated agenesis of the corpus callosum (ACC) are associated with a broad spectrum of neurodevelopmental disability that cannot be specifically predicted in prenatal neuroimaging. We hypothesized that ACC may be associated with aberrant cortical folding. In this study, we determined altered patterning of early primary sulci development in fetuses with isolated ACC using novel quantitative sulcal pattern analysis which measures deviations of regional sulcal features (position, depth, and area) and their intersulcal relationships in 7 fetuses with isolated ACC (27.1 ± 3.8 weeks of gestation, mean ± SD) and 17 typically developing (TD) fetuses (25.7 ± 2.0 weeks) from normal templates. Fetuses with ACC showed significant alterations in absolute sulcal positions and relative intersulcal positional relationship compared to TD fetuses, which were not detected by traditional gyrification index. Our results reveal altered sulcal positional development even in isolated ACC that is present as early as the second trimester and continues throughout the fetal period. It might originate from altered white matter connections and portend functional variances in later life.

Magnetic resonance imaging as an alternative to computed tomography in select patients with traumatic brain injury: a retrospective comparison.

OBJECT: Traumatic head injury (THI) is a highly prevalent condition in the United States, and concern regarding excess radiation-related cancer mortality has placed focus on limiting the use of CT in the evaluation of pediatric patients with THI. Given the success of rapid-acquisition MRI in the evaluation of ventriculoperitoneal shunt malfunction in pediatric patient populations, this study sought to evaluate the sensitivity of MRI in the setting of acute THI. METHODS: Medical records of 574 pediatric admissions for THI to a Level 1 trauma center over a 10-year period were retrospectively reviewed to identify patients who underwent both CT and MRI examinations of the head within a 5-day period. Thirty-five patients were found, and diagnostic images were available for 30 patients. De-identified images were reviewed by a neuroradiologist for presence of any injury, intracranial hemorrhage, diffuse axonal injury (DAI), and skull fracture. Radiology reports were used to calculate interrater reliability scores. Baseline demographics and concordance analysis was performed with Stata version 13. RESULTS: The mean age of the 30-patient cohort was 8.5 ± 6.7 years, and 63.3% were male. The mean Injury Severity Score was 13.7 ± 9.2, and the mean Glasgow Coma Scale score was 9 ± 5.7. Radiology reports noted 150 abnormal findings. CT scanning missed findings in 12 patients; the missed findings included DAI (n = 5), subarachnoid hemorrhage (n = 6), small subdural hematomas (n = 6), cerebral contusions (n = 3), and an encephalocele. The CT scan was negative in 3 patients whose subsequent MRI revealed findings. MRI missed findings in 13 patients; missed findings included skull fracture (n = 5), small subdural hematomas (n = 4), cerebral contusions (n = 3), subarachnoid hemorrhage (n = 3), and DAI (n = 1). MRI was negative in 1 patient whose preceding CT scan was read as positive for injury. Although MRI more frequently reported intracranial findings than CT scanning, there was no statistically significant difference between CT and MRI in the detection of any intracranial injury (p = 0.63), DAI (p = 0.22), or intracranial hemorrhage (p = 0.25). CT scanning tended to more frequently identify skull fractures than MRI (p = 0.06). CONCLUSIONS: MRI may be as sensitive as CT scanning in the detection of THI, DAI, and intracranial hemorrhage, but missed skull fractures in 5 of 13 patients. MRI may be a useful alternative to CT scanning in select stable patients with mild THI who warrant neuroimaging by clinical decision rules.

Twists and turns of determining amyloid type and amyloid-related organ damage: discordance and clinical skepticism in the era of proteomic typing.

Systemic immunoglobulin light-chain primary amyloidosis (AL) is the most common type of systemic amyloidosis. Recent advances in AL amyloidosis include the use of definitive proteomic typing, confirming the type of amyloid in patients with two possible amyloid-forming proteins. Laser microdissection followed by mass spectrometry (LMD/MS) can correctly identify the amyloid type with over 95% sensitivity and specificity. We report the case of a 68-year-old man with a history of IgA lambda monoclonal gammopathy and peripheral neuropathy who was diagnosed with pelvic nodal and psoas amyloidosis. The amyloid was found to be AL kappa type by LMD/MS. While LMD/MS has been effective in distinguishing among AL, secondary amyloidosis and hereditary forms of amyloidosis, our case demonstrates that typing can also identify unusual instances of discordance between light chain isotypes associated with clonal processes.

Incomplete stent apposition in Enterprise stent-mediated coiling of aneurysms: persistence over time and risk of delayed ischemic events.

OBJECT: Incomplete stent apposition of the closed cell-design Enterprise stent following stent-mediated coil embolization of intracranial aneurysms has been associated with increased risk of periprocedural thromboembolic events. In this study, the authors seek to determine the natural history of incomplete stent apposition and evaluate the clinical implications of the phenomenon. METHODS: Since January 2009, all patients receiving Enterprise stents in the treatment of intracranial aneurysms at the authors' institution have undergone serial 3-T MRI with incomplete stent apposition identified by the crescent sign on multiplanar reconstructions of MR angiograms. Magnetic resonance images and MR angiograms obtained at 3, 9, and 18 months after stent-assisted coil embolization were analyzed along with admission and follow-up clinical medical records. These records were evaluated for any radiographic and clinical, transient or permanent ischemic neurological events. RESULTS: Fifty patients receiving Enterprise stents were eligible for inclusion and analysis in the study. Incomplete stent apposition was identified in postoperative imaging studies in 22 (44%) of 50 patients, with 19 (86%) of 22 crescent signs persisting and 3 (14%) of 22 crescent signs resolving on subsequent serial imaging. Delayed ischemic events occurred in 8 (16%) of 50 cases, and all cases involved patients with incomplete stent apposition. The events were transient ischemic attacks (TIAs) in 5 cases, asymptomatic radiographic strokes in 2 cases, and symptomatic strokes and TIAs in the final case. There were no delayed ischemic events in patients who did not have incomplete stent apposition. Only 1 of the delayed ischemic events (2%) was permanent and symptomatic. The postoperative presence of a crescent sign and persistence of the crescent sign were both significantly associated with delayed ischemic events (p < 0.001 and p = 0.002, respectively). CONCLUSIONS: Incomplete stent apposition is a temporally persistent phenomenon, which resolves spontaneously in only a small minority of cases and appears to be a risk factor for delayed ischemic events. Although further follow-up is needed, these results suggest that longer duration of antiplatelet therapy and clinical follow-up may be warranted in cases of recognized incomplete stent apposition.