[Show abstract][Hide abstract] ABSTRACT: It has been hypothesized that [18F]-sodium fluoride (NaF) uptake imaged with positron emission tomography (PET) binds to hydroxyapatite molecules expressed in regions with active calcification. Therefore, we aimed to validate NaF as a marker of hydroxyapatite expression in high-risk carotid plaque.
Eleven patients (69 ± 5 years, 3 female) scheduled for carotid endarterectomy were prospectively recruited for NaF PET/CT. One patient received a second contralateral endarterectomy; two patients were excluded (intolerance to contrast media and PET/CT misalignment). The bifurcation of the common carotid was used as the reference point; NaF uptake (tissue to blood ratio - TBR) was measured at every PET slice extending 2 cm above and below the bifurcation. Excised plaque was immunostained with Goldner’s Trichrome and whole-slide digitized images were used to quantify hydroxyapatite expression. Pathology was co-registered with PET.
NaF uptake was related to the extent of hydroxyapatite expression (r=0.45, p<0.001). Upon classifying bilateral plaque for symptomatology, symptomatic plaque was associated with cerebrovascular events (3.75±1.1 TBR, n=9) and had greater NaF uptake than clinically silent asymptomatic plaque (2.79±0.6 TBR, n=11) (p=0.04).
NaF uptake is related to hydroxyapatite expression and is increased in plaque associated with cerebrovascular events. NaF may serve as a novel biomarker of active calcification and plaque vulnerability.
Full-text · Article · May 2015 · The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques
[Show abstract][Hide abstract] ABSTRACT: Whole-slide scanning of tissue sections spatially informed by imaging studies offers the opportunity to reconstruct specimens for co-registration to 3D imaging data. Digital image analysis algorithms can be designed to analyze and reconstruct such specimens via electronic “pipelines”.
A goal of the Canadian Atherosclerosis Imaging Network (CAIN) is to improve the assessment of carotid atheromatous disease through studies that inform clinical imaging with gold-standard data (plaque pathology). To achieve this, sectioned atheromas are manually annotated and analyzed by electronic algorithm for pathological features of interest. Resulting images are then reassembled in 3D for registration to ultrasound, CT, PET-CT and MRI studies.
Carotid endarterectomy specimens were sub-serially sectioned, stained, digitized and annotated manually and by electronic algorithms. Resulting 2D images were successfully rendered, reassembled and analyzed in 3D using ex-vivo micro-CT as a spatial reference. Furthermore, histology quantification using colour deconvolution was found to be preferred over hue-saturation-intensity methods 94.7-100% of the time in a blinded multiple rater study.
Automated “pipelines” greatly facilitate 3D reconstruction in comparison to traditional slice-by-slice methods. Transformations spatially guided by pre-existing imaging data is not only faster, but has superior objectivity and fidelity. With embedded annotations, 3D pathology maps become a rich, micron-level, permanent digital pathological database for correlative studies.
No preview · Article · May 2015 · The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques
[Show abstract][Hide abstract] ABSTRACT: Gout is a rheumatological disorder found exclusively in human species. It is caused by deposition of crystals of monosodium urate in joints, cartilages, tendons, and soft tissues. Involvement of the spine, however, is rare. In this report, we describe two patients presented to King Abdulaziz Medical City in Jeddah with clinical features of cervical myelopathy, including neck pain, L'hermitte phenomena, quadriparesis and sensory deficit (shoulder level). Magnetic resonance imaging confirmed the presence of cervical cord compression with intrinsic cord signal abnormalities. Both patients had laminectomy and intraoperatively; severe canal stenosis was identified. A whitish cheesy material was noticed causing significant root compression. The pathology was diagnostic of gout. In this article, we present two difficult cases with interesting clinical, radiological and pathological findings. We emphasize on the importance of early diagnosis to prevent morbidity.
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to describe a series of patients with pathologically proven chronic encephalitis who had a nonprogressive course during a long follow-up, suggestive of a "benign" variant of Rasmussen's encephalitis (RE).
Four patients who were referred to our Comprehensive Epilepsy Program at London Health Science Centre in London, Ontario, were diagnosed with chronic encephalitis on a pathological basis after epilepsy surgery to treat their partial-onset seizures.
None of our four cases followed the typical course of RE despite their childhood-onset seizures between ages 2 and 12years. One was preceded by a mild head trauma and fever at onset. None had epilepsia partialis continua (EPC). Their long-term follow-up revealed a nonprogressive form of the syndrome with respect to the neurological examination, EEG, MRI, and neuropsychological findings.
These cases extend the spectrum of childhood-onset intractable epilepsy with chronic encephalitis to include nonprogressive variants of RE. The absence of EPC may be a prognostic indicator of a nonprogressive course.
Full-text · Article · Dec 2013 · Epilepsy & Behavior
[Show abstract][Hide abstract] ABSTRACT: Adult-onset leukodystrophies are clinically and pathologically heterogeneous diseases, and the overlapping morphologic features among these disorders can lead to confusion in pathologic classification. We report 3 recent autopsy cases that illustrate the clinicopathologic distinction between the 3 entities. The first, autosomal dominant leukodystrophy, is characterized clinically by early autonomic dysfunction and genetically by LMNB1 (lamin B1 gene) duplication. Recently, another clinical subtype emerged without the early autonomic dysfunction but with a similar genetic abnormality documented in 1 family. We reviewed the reported autopsy cases and show that both clinical subtypes share distinctive pathologic features. Other forms of adult-onset leukodystrophy can be classified based on the histologic evidence of the primary pathologic processes. A case of axonopathy with secondary demyelination serves as a prototype for adult-onset leukoencephalopathy/leukodystrophy with axonal spheroids; the genetic mutation of CSF1R (colony stimulating factor 1R) was recently discovered in patients with this disorder. A case of a primary demyelinating disease with no other distinctive pathologic features is designated as orthochromatic leukodystrophy. Pigmented glia can be present in both of the latter two categories and should not be used as a differentiating diagnostic feature. Based on the observations of our cases and literature review, we propose an algorithm for a practical diagnostic approach to adult-onset leukodystrophies.
[Show abstract][Hide abstract] ABSTRACT: We developed novel methodology for investigating the use of quantitative relaxometry (T1, T2) and diffusion tensor imaging (DTI) for lateralization in temporal lobe epilepsy. Patients with mesial temporal sclerosis confirmed by pathology (N = 8) and non-MTS unilateral temporal lobe epilepsy (N = 6) were compared against healthy controls (N = 19) using voxel-based analysis restricted to the anterior temporal lobes, and laterality indices for each MRI metric (T1, T2, fractional anisotropy (FA), mean diffusivity, axial and radial diffusivity) were computed based on the proportion of significant voxels on each side. The diffusivity metrics were the most lateralizing MRI metrics in MTS and non-MTS subsets, with significant differences also seen with FA, T1 and T2. Patient-specific multi-modal laterality indices were also computed and were shown to clearly separate the left-onset and right-onset patients. Marked differences between left-onset and right-onset patients were also observed, with left-onset patients exhibiting stronger laterality indices. Finally, neocortical abnormalities were found to be more common in the non-MTS patients. These preliminary results on a small sample size support the further investigation of quantitative MRI and multi-modal image analysis in clinical determination of seizure onset. The presence of more neocortical abnormalities in the non-MTS group suggests a role in seizure onset or propagation and motivates the investigation of more sensitive histopathological analysis to detect and delineate potentially subtle neocortical pathology.
No preview · Article · Jan 2013 · Epilepsy research