Integrating EM and Patch-seq data: Synaptic connectivity and target specificity of predicted Sst transcriptomic types.

Neural circuit function is shaped both by the cell types that comprise the circuit and the connections between those cell types 1 . Neural cell types have previously been defined by morphology 2, 3 , electrophysiology 4, 5 , transcriptomic expression 6-8 , connectivity 9-13 , or even a combination of such modalities 14-16 . More recently, the Patch-seq technique has enabled the characterization of morphology (M), electrophysiology (E), and transcriptomic (T) properties from individual cells 17-20 . Using this technique, these properties were integrated to define 28, inhibitory multimodal, MET-types in mouse primary visual cortex 21 . It is unknown how these MET-types connect within the broader cortical circuitry however. Here we show that we can predict the MET-type identity of inhibitory cells within a large-scale electron microscopy (EM) dataset and these MET-types have distinct ultrastructural features and synapse connectivity patterns. We found that EM Martinotti cells, a well defined morphological cell type 22, 23 known to be Somatostatin positive (Sst+) 24, 25 , were successfully predicted to belong to Sst+ MET-types. Each identified MET-type had distinct axon myelination patterns and synapsed onto specific excitatory targets. Our results demonstrate that morphological features can be used to link cell type identities across imaging modalities, which enables further comparison of connectivity in relation to transcriptomic or electrophysiological properties. Furthermore, our results show that MET-types have distinct connectivity patterns, supporting the use of MET-types and connectivity to meaningfully define cell types.

Altered gene expression in the dorsolateral prefrontal cortex of individuals with schizophrenia.

The underlying pathology of schizophrenia (SZ) is likely as heterogeneous as its symptomatology. A variety of cortical and subcortical regions, including the prefrontal cortex, have been implicated in its pathology, and a number of genes have been identified as risk factors for disease development. We used in situ hybridization (ISH) to examine the expression of 58 genes in the dorsolateral prefrontal cortex (DLPFC, comprised of Brodmann areas 9 and 46) from 19 individuals with a premorbid diagnosis of SZ and 33 control individuals. Genes were selected based on: (1) previous identification as risk factors for SZ; (2) cell type markers or (3) laminar markers. Cell density and staining intensity were compared in the DLPFC, as well as separately in Brodmann areas 9 and 46. The expression patterns of a variety of genes, many of which are associated with the GABAergic system, were altered in SZ when compared with controls. Additional genes, including C8orf79 and NR4A2, showed alterations in cell density or staining intensity between the groups, highlighting the need for additional studies. Alterations were, with only a few exceptions, limited to Brodmann area 9, suggesting regional specificity of pathology in the DLPFC. Our results agree with previous studies on the GABAergic involvement in SZ, and suggest that areas 9 and 46 may be differentially affected in the disease. This study also highlights additional genes that may be altered in SZ, and indicates that these potentially interesting genes can be identified by ISH and high-throughput image analysis techniques.

Staging of laryngeal cancer using 64-channel multidetector row CT: comparison of standard neck CT with dedicated breath-maneuver laryngeal CT.

BACKGROUND AND PURPOSE: With a 64-channel multidetector row CT, imaging acquisition during speech, swallowing, or phonation has become feasible. However, the actual benefit of these additional focused images should be critically evaluated with respect to radiation dose. The purpose of this study was to determine if dedicated laryngeal CT using breath-holding and straw-blowing improved the accuracy of TNM-staging for patients with biopsy-proved laryngeal carcinomas in comparison with a standard neck CT. MATERIALS AND METHODS: A total of 27 patients underwent a standard neck CT and a laryngeal CT with additional images acquired while patients held their breath or blew through a straw. Two radiologists interpreted the neck CT and later the laryngeal CT and assigned a TNM-stage for each case. These interpretations were compared with a TNM-stage determined by surgery and/or clinical examination for the individual patients. The accuracy of standard neck CT was compared with the accuracy of laryngeal CT. RESULTS: The overall accuracy was not significantly different between standard neck CT and the additional laryngeal CT and was, in fact, lower in cases with additional larynx images. The accuracy of staging was slightly improved with the additional laryngeal CT for glottic cancers; however, it was decreased for supraglottic cancers. The accuracy of a dichotomous diagnosis of early-versus-advanced-stage cancer was 0.86 for the standard neck CT and 0.80 for the laryngeal CT. The readers' confidence levels did not improve with the use of the additional images. CONCLUSIONS: In the era of isovoxel multidetector CT technology and judicious monitoring of radiation dose, a standard neck CT with coronal and sagittal reformats should suffice for the staging of laryngeal cancer.

Fibrous histiocytoma and fibrous tissue tumors of the orbit.

Fibrous orbital tumors present clinically and radiographically in a broad spectrum ranging from a benign mass, to locally aggressive tumor, to invasive malignancy. Pathologic analysis and diagnosis are often challenging, usually based on a combination of light microscopy, immunohistochemistry, and electron microscopic findings. Some light microscopic and immunohistochemical findings, however, are relatively characteristic. A storiform or cartwheel pattern and vimentin staining are characteristic of fibrous histiocytoma. A herringbone pattern is usually found in fibrosarcoma. A "patternless pattern" and CD34 staining is found most commonly in solitary fibrous tumor. CT and MR imaging findings, as well as clinical presentation, in fibrous orbital lesions are often difficult to distinguish from those of other orbital masses, although there may be useful clues. Benign fibrous lesions are usually well-circumscribed and may chronically remodel bone, whereas more aggressive malignant fibrous tumors tend to have infiltrating margins and may destroy bone on CT or MR imaging. With malignant fibrous masses, enhancement patterns on CT or MR imaging may be more inhomogeneous, with avascular or necrotic nonenhancing regions. At MR imaging, benign lesions tend to be homogeneous on T1, T2, and postgadolinium T1-weighted images, whereas malignant soft tissue lesions may change their pattern from homogeneous on T1-weighted images to heterogeneous with low signal septations on T2-weighted images. Low T2 signal comprising part or all of a fibrous lesion correlates with dense collagen fibers, with a less cellular matrix. Areas of hyperintensity on T2-weighted images correspond with a more cellular matrix of fibroblasts and other cells. Calcification within a tumor, however, may give a similar appearance. Thus, if a lesion has predominantly low signal on T2-weighted images, or less specifically has low signal septations, then a fibrous orbital lesion with high collagen content may be ranked higher in the differential diagnosis (see Figs. 2E and 3B). When T2 signal is intermediate-to-high, then one has a difficult time narrowing the differential diagnosis. Radiographically, distinguishing these lesions from other fibrous orbital lesions, as well as from other varieties of orbital masses, is difficult. Differential diagnosis of fibrous orbital masses includes all the fibrous lesions described in this article, in addition to schwannoma (Fig. 7), neurofibroma (Figs. 4 and 8), hemangiopericytoma (Figs. 9 and 10), rhabdomyosarcoma, meningioma, lymphoma, and metastasis (Figs. 11 and 12). A history of prior orbital irradiation for retinoblastoma or other tumors may raise the possibility of radiation-induced secondary tumors, such as MFH, fibrosarcoma, and osteosarcoma. Determining the extent of orbital involvement remains the primary goal of the radiologist. The final diagnosis still rests with the pathologist.

Comparison of CT and MR imaging in staging of neck metastases.

PURPOSE: To compare the abilities of magnetic resonance (MR) imaging and computed tomography (CT) in detection of lymph node metastasis from head and neck squamous cell carcinoma. MATERIALS AND METHODS: MR imaging and CT were performed with standard protocols in patients with known carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx. Histopathologic examination was performed to validate imaging findings. Between 1991 and 1994, 213 patients undergoing 311 neck dissections were accrued at three institutions. RESULTS: For the upper jugular and spinal accessory regions, the areas under the receiver operating characteristic curves for combined information on size and internal abnormality were 0.80 for CT and 0.75 for MR imaging. Sensitivities, specificities, negative predictive values (NPVs), and positive predictive values (PPVs) were calculated for various size criteria with and without internal abnormality information. With use of a 1-cm size or an internal abnormality to indicate a positive node, CT had an NPV of 84% and a PPV of 50%, and MR imaging had an NPV of 79% and a PPV of 52%. CT achieved an NPV of 90%, correlating with a PPV of 44%, with use of 5-mm size as an indicator of a positive node. CONCLUSION: CT performed slightly better than MR imaging for all interpretative criteria. However, a high NPV was achieved only when a low size criterion was used and was therefore associated with a relatively low PPV.

Lesions and nodes of the thoracic inlet.

The anatomy of the thoracic inlet and lesions of the thyroid gland, parathyroid glands, and brachial plexus are discussed in depth in other articles in this issue. The focus of this article is to review lesions of the remaining structures and spaces that abut or traverse through the plane of the thoracic inlet. Although this junction of the neck with the chest is relatively easy to define on coronal or sagittal MR, determining this level with axial CT and MR is actually a bit of a challenge. Depending on neck length, degree of neck extension, shoulder thickness, arm position, thoracic kyphosis, and scan angle, the appearance of this area is extremely variable. For the purpose of this article, the thoracic inlet is better regarded as a zone or volume extending several centimeters both above and below this plane. In addition, this zone is very prone to CT beam hardening artifacts from the thickness of the shoulders as well as MR pulsation, respiratory, and bulk susceptibility artifacts, often resulting in less than esthetic images.

Phased-array surface coil MR of the orbits and optic nerves.

PURPOSE: To devise a practical technique for high-resolution evaluation of the anterior optic apparatus using a phased-array surface coil system, and to evaluate this system in patients with suspected optic pathway abnormalities. METHODS: A four-element phased-array coil pair was placed on each side of the head, and signal-to-noise measurements were obtained using a head phantom. Comparison between the phased-array coil, the quadrature coil, and a single-turn 12.7-cm (5-in) surface coil was done. T1 spin-echo and T2 fast spin-echo sequences were obtained in the oblique axial and oblique sagittal planes, to approximate the long axis of the optic nerves and the nonoblique coronal plane. RESULTS: The phantom signal-to-noise measurements at simulated locations of the optic nerve head, optic canal, and optic chiasm revealed an improvement of at least 30% using the phased-array system. Of 24 imaged cases, 9 had trauma, 5 had suspected neoplasms, and 2 had optic neuritis. In 3 patients, an unexpected diagnosis of optic pathway contusion or infarction was made. The remaining 8 patients had various suspected visual pathway lesions. CONCLUSION: Phased-array surface coils allow rapid, thin-section imaging of the entire anterior optic pathway, with improved signal-to-noise ratio. This may improve evaluation of optic pathway lesions over conventional techniques.

Nasal and paranasal sinus anomalies in children with chronic sinusitis.

Functional endoscopic sinus surgery (FESS) is being advocated to treat children with chronic sinusitis. The surgeon performing FESS needs an intimate understanding of the anatomy to adequately treat disease and avoid complications. One hundred thirty-six patients who had endoscopic sinus surgery were reviewed. Preoperative direct coronal computed tomography scans were available for review in 114 patients. Several nasal and paranasal sinus anomalies were uncovered during this evaluation. The most common was hypoplasia of the maxillary sinuses. All hypoplastic maxillary sinuses had diseased mucosa. Eleven patients were found to have a laterally deviated uncinate process and abnormal anatomy of the maxillary ostia. Other anomalies such as concha bullosa, Haller's cells, and paradoxic curvature of the middle turbinate were found, and their respective frequencies in this population were determined.

Brain SPECT and the effect of cerebral angioplasty in delayed ischemia due to vasospasm.

Cerebral vasospasm is a major determinant of outcome after subarachnoid hemorrhage (SAH). Brain SPECT with 99mTc-HMPAO was obtained before and after cerebral angioplasty in 10 patients with delayed ischemia due to vasospasm. Eight patients had clinically evident neurologic improvement after the procedure. Visual interpretation and an internal-reference (cerebellum), manual, semi-quantitative region of interest (ROI) analysis revealed improvement of regional cerebral blood flow (rCBF) in 9 out of 10. There were disagreements between the visual and ROI analysis in the two that did not improve clinically. For all 10, the average increase per anterior circulation vessel dilated (n = 17) was 8.8% by comparison of the corticocerebellar ratios. For the eight that improved, the average increase was 10.5%. Brain SPECT is valuable for evaluating delayed cerebral ischemia caused by vasospasm after SAH and is useful to document the changes in rCBF induced by angioplasty. It is possible that SPECT may be useful to detect critical reductions in perfusion before clinical deficits develop, thereby offering the potential to identify candidates for early treatment with angioplasty.

Brain SPECT and transcranial doppler ultrasound in vasospasm-induced delayed cerebral ischemia after subarachnoid hemorrhage.

Clinical vasospasm, or delayed ischemia-related neurologic deficits, is the prime determinant of morbidity and mortality after subarachnoid hemorrhage. The diagnosis of clinical vasospasm has been based mainly on clinical observations. Noninvasive techniques for evaluating vasospasm have great promise in supplementing the detailed neurologic examination and assessing the effects of therapy. The clinical utility of single-photon emission computed tomography (SPECT) of regional cerebral blood flow and transcranial Doppler ultrasound (TCD) in the evaluation of cerebral vasospasm after subarachnoid hemorrhage was reviewed in 40 patients. The combination of these noninvasive tests was valuable for the investigation of the dynamic anatomic and functional aspects of vasospasm. TCD proved helpful in monitoring for vascular narrowing by measurements of blood flow velocity. Brain SPECT ascertained the effects of vasospasm on regional cerebral blood flow. In the diagnosis of clinical vasospasm, or delayed ischemic deficits, brain SPECT was more sensitive and specific than TCD. The combination of SPECT and TCD was useful in the assessment of the effect of cerebral angioplasty on hemodynamics and perfusion in the attempt to avert infarction.

Optimizing brain MR imaging protocols with gadopentetate dimeglumine: enhancement of intracranial lesions on spin-density- and T2-weighted images.

To determine whether long TR MR imaging is best performed before or after IV administration of gadopentetate dimeglumine, we obtained spin-density- and T2-weighted images before and after contrast administration in 21 patients with known intracranial enhancing lesions. Of 25 lesions demonstrating enhancement on T1-weighted sequences, 21 showed mild or moderate enhancement on spin-density-weighted sequences and 20 showed mild enhancement on T2-weighted sequences. Importantly, no spin-density or T2 information was obscured by the administration of gadopentetate dimeglumine, and no T2 shortening effects were visible. Two new foci of enhancement were visible on postcontrast spin-density- and T2-weighted images that were missed on postcontrast T1-weighted images and on precontrast spin-density- and T2-weighted studies. Visualization of new areas of enhancement is the main advantage provided by the long TR images obtained after IV injection of gadopentetate dimeglumine. The most likely reason for the appearance of these newly visualized lesions is thought to be delayed enhancement. This imaging protocol also allows the display of adjacent edema or gliosis and enhancing lesions on a single image. Additionally, in three cases, posterior fossa phase-shift artifacts raised the suspicion of an enhancing lesion on postcontrast T1-weighted images, but the cerebellum was shown to be normal on the postcontrast spin-density- and T2-weighted studies. On the basis of our results, we recommend obtaining long TR images after rather than before the administration of gadopentetate dimeglumine in patients with intracranial enhancing lesions.

Myocutaneous flap failure: early detection with Gd-DTPA-enhanced MR imaging.

Magnetic resonance (MR) imaging was used to evaluate myocutaneous flap viability in an animal model. Bilateral myocutaneous panniculus carnosus groin flaps were created in 14 piglets. Eight of the piglets underwent early occlusion of the vascular pedicle to one flap that resulted in flap failure in all cases. Six piglets underwent late occlusion of the vascular pedicle to one flap that resulted in flap survival in all cases. Spin-echo T1- and T2-weighted MR images were obtained from all piglets 2 and 24 hours after occlusion. Additional gadolinium diethylene-triaminepentaacetic acid (DTPA)-enhanced serial T1-weighted images were obtained in four piglets who underwent early occlusion and in four piglets who underwent late occlusion of the pedicle. The T2-weighted images showed increased signal intensity in both occluded and control flaps and thus did not help predict flap viability. Gd-DTPA-enhanced images enabled accurate prediction of flap viability. The images of early-occluded (non-viable) flaps demonstrated no contrast material enhancement, while both the late-occluded (viable) flaps and the control flaps were contrast enhanced. The authors conclude that Gd-DTPA-enhanced MR imaging can help predict myocutaneous flap viability in piglets.

Supratentorial and spinal cord hemangioblastomas: gadolinium enhanced MR appearance with pathologic correlation.

A case is presented that illustrates the magnetic resonance appearance of supratentorial hemangioblastomas both prior to and following intravenous administration of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA). Spinal cord hemangioblastomas were also present and were visualized only after Gd-DTPA administration. Pathological verification of the multiple tumoral lesions was obtained.

Globe tenting: a sign of increased orbital tension.

Globe tenting is a change in the posterior globe configuration that results in a tented or conical appearance and is objectively defined as a posterior globe angle of less than 130 degrees. Globe tenting is caused by an acute/subacute intraorbital mass effect producing significant proptosis with tethering of the globe by the stretched optic nerve. In this series of 10 patients, globe tenting was produced by subperiosteal abscess (five cases), hemorrhage into a lymphangioma (two cases), a varix (one case), traumatic carotid hemorrhage into a lymphangioma (two cases), a varix (one case), traumatic carotid cavernous fistula (one case), and multiple epithelial implantation cysts (one case). Progressive narrowing of the posterior globe angle correlated with an increase in proptosis and in optic nerve length, as well as with more severe visual impairment. Tenting with a posterior globe angle of 120-130 degrees correlated with mild visual symptoms and a good recovery. A posterior globe angle of less than 120 degrees with acute proptosis constitutes a surgical emergency; a delay in surgical decompression in these patients may prevent complete recovery of visual function. CT is useful in providing good characterization of globe tenting and, thus, in helping to determine the clinical significance of this abnormality.

Computed tomography of calvarial and petrous bone sarcoidosis.

This report describes the radiographic features in a case of sarcoidosis involving both the frontal calvaria and the petrous bone. The plain radiographic and nuclear medicine findings were consistent with previous descriptions. High resolution CT demonstrated concentric growth with a lucent advancing margin, ghost-like remnant of partially replaced bone, crossing of suture lines, invasion of contiguous bones, and lack of associated soft tissue mass.

Computed tomography of anterior inferior cerebellar artery aneurysm mimicking an acoustic neuroma.

Twenty-one previously reported cases of aneurysms of the anterior inferior cerebellar artery (AICA) were reviewed. They often present acutely with subarachnoid hemorrhage due to rupture, or less frequently with an insidious onset, as a cerebellopontine angle (CPA) mass. Rupture of the aneurysm is usually not difficult to diagnose because of the acute symptoms and the subarachnoid hemorrhage, which can easily be detected by CT or lumbar puncture. However, caution must be exercised in those lesions presenting as a CPA mass clinically, which on CT appear unusually dense with contrast enhancement. Erosion of the internal auditory canal may be present but is non-specific. If an enhancing CPA mass appears atypical and dynamic CT confirms rapid enhancement, vertebrobasilar angiography is essential to establish an AICA aneurysm as the cause.

Computed tomography of a cerebellopontine angle lipoma.

In this report we document the clinical, radiologic, surgical, and pathologic features of a cerebellopontine angle (CPA) lipoma, including the CT visualization of the seventh and eighth cranial nerves passing through the middle of the lesion, a feature previously undescribed. Comparison is made with other reported CPA lipomas.