Indirect 1H-[13C] MRS of the human brain at 7 T using a 13C-birdcage coil and eight transmit-receive 1H-dipole antennas with a 32-channel 1H-receive array.

The neuronal tricarboxylic acid and glutamate/glutamine (Glu/Gln) cycles play important roles in brain function. These processes can be measured in vivo using dynamic 1H-[13C] MRS during administration of 13C-labeled glucose. Proton-observed carbon-edited (POCE) MRS enhances the signal-to-noise ratio (SNR) compared with direct 13C-MRS. Ultra-high field further boosts the SNR and increases spectral dispersion; however, even at 7 T, Glu and Gln 1H-resonances may overlap. Further gain can be obtained with selective POCE (selPOCE). Our aim was to create a setup for indirect dynamic 1H-[13C] MRS in the human brain at 7 T. A home-built non-shielded transmit-receive 13C-birdcage head coil with eight transmit-receive 1H-dipole antennas was used together with a 32-channel 1H-receive array. Electromagnetic simulations were carried out to ensure that acquisitions remained within local and global head SAR limits. POCE-MRS was performed using slice-selective excitation with semi-localization by adiabatic selective refocusing (sLASER) and stimulated echo acquisition mode (STEAM) localization, and selPOCE-MRS using STEAM. Sequences were tested in a phantom containing non-enriched Glu and Gln, and in three healthy volunteers during uniformly labeled 13C-glucose infusions. In one subject the voxel position was alternated between bi-frontal and bi-occipital placement within one session. [4-13C]Glu-H4 and [4-13C]Gln-H4 signals could be separately detected using both STEAM-POCE and STEAM-selPOCE in the phantom. In vivo, [4,5-13C]Glx could be detected using both sLASER-POCE and STEAM-POCE, with similar sensitivities, but [4,5-13C]Glu and [4,5-13C]Gln signals could not be completely resolved. STEAM-POCE was alternately performed bi-frontal and bi-occipital within a single session without repositioning of the subject, yielding similar results. With STEAM-selPOCE, [4,5-13C]Glu and [4,5-13C]Gln could be clearly separated. We have shown that with our setup indirect dynamic 1H-[13C] MRS at 7 T is feasible in different locations in the brain within one session, and by using STEAM-selPOCE it is possible to separate Glu from Gln in vivo while obtaining high quality spectra.

Synthetic MRI with Magnetic Resonance Spin TomogrAphy in Time-Domain (MR-STAT): Results from a Prospective Cross-Sectional Clinical Trial.

BACKGROUND: Magnetic Resonance Spin TomogrAphy in Time-domain (MR-STAT) can reconstruct whole-brain multi-parametric quantitative maps (eg, T1 , T2 ) from a 5-minute MR acquisition. These quantitative maps can be leveraged for synthetization of clinical image contrasts. PURPOSE: The objective was to assess image quality and overall diagnostic accuracy of synthetic MR-STAT contrasts compared to conventional contrast-weighted images. STUDY TYPE: Prospective cross-sectional clinical trial. POPULATION: Fifty participants with a median age of 45 years (range: 21-79 years) consisting of 10 healthy participants and 40 patients with neurological diseases (brain tumor, epilepsy, multiple sclerosis or stroke). FIELD STRENGTH/SEQUENCE: 3T/Conventional contrast-weighted imaging (T1 /T2 weighted, proton density [PD] weighted, and fluid-attenuated inversion recovery [FLAIR]) and a MR-STAT acquisition (2D Cartesian spoiled gradient echo with varying flip angle preceded by a non-selective inversion pulse). ASSESSMENT: Quantitative T1 , T2 , and PD maps were computed from the MR-STAT acquisition, from which synthetic contrasts were generated. Three neuroradiologists blinded for image type and disease randomly and independently evaluated synthetic and conventional datasets for image quality and diagnostic accuracy, which was assessed by comparison with the clinically confirmed diagnosis. STATISTICAL TESTS: Image quality and consequent acceptability for diagnostic use was assessed with a McNemar's test (one-sided α = 0.025). Wilcoxon signed rank test with a one-sided α = 0.025 and a margin of Δ = 0.5 on the 5-level Likert scale was used to assess non-inferiority. RESULTS: All data sets were similar in acceptability for diagnostic use (≥3 Likert-scale) between techniques (T1 w:P = 0.105, PDw:P = 1.000, FLAIR:P = 0.564). However, only the synthetic MR-STAT T2 weighted images were significantly non-inferior to their conventional counterpart; all other synthetic datasets were inferior (T1 w:P = 0.260, PDw:P = 1.000, FLAIR:P = 1.000). Moreover, true positive/negative rates were similar between techniques (conventional: 88%, MR-STAT: 84%). DATA CONCLUSION: MR-STAT is a quantitative technique that may provide radiologists with clinically useful synthetic contrast images within substantially reduced scan time. EVIDENCE LEVEL: 1 Technical Efficacy: Stage 2.

CXCR4 expression in glioblastoma tissue and the potential for PET imaging and treatment with [68Ga]Ga-Pentixafor /[177Lu]Lu-Pentixather.

PURPOSE: CXCR4 (over)expression is found in multiple human cancer types, while expression is low or absent in healthy tissue. In glioblastoma it is associated with a poor prognosis and more extensive infiltrative phenotype. CXCR4 can be targeted by the diagnostic PET agent [68Ga]Ga-Pentixafor and its therapeutic counterpart [177Lu]Lu-Pentixather. We aimed to investigate the expression of CXCR4 in glioblastoma tissue to further examine the potential of these PET agents. METHODS: CXCR4 mRNA expression was examined using the R2 genomics platform. Glioblastoma tissue cores were stained for CXCR4. CXCR4 staining in tumor cells was scored. Stained tissue components (cytoplasm and/or nuclei of the tumor cells and blood vessels) were documented. Clinical characteristics and information on IDH and MGMT promoter methylation status were collected. Seven pilot patients with recurrent glioblastoma underwent [68Ga]Ga-Pentixafor PET; residual resected tissue was stained for CXCR4. RESULTS: Two large mRNA datasets (N = 284; N = 540) were assesed. Of the 191 glioblastomas, 426 cores were analyzed using immunohistochemistry. Seventy-eight cores (23 tumors) were CXCR4 negative, while 18 cores (5 tumors) had both strong and extensive staining. The remaining 330 cores (163 tumors) showed a large inter- and intra-tumor variation for CXCR4 expression; also seen in the resected tissue of the seven pilot patients-not directly translatable to [68Ga]Ga-Pentixafor PET results. Both mRNA and immunohistochemical analysis showed CXCR4 negative normal brain tissue and no significant correlation between CXCR4 expression and IDH or MGMT status or survival. CONCLUSION: Using immunohistochemistry, high CXCR4 expression was found in a subset of glioblastomas as well as a large inter- and intra-tumor variation. Caution should be exercised in directly translating ex vivo CXCR4 expression to PET agent uptake. However, when high CXCR4 expression can be identified with [68Ga]Ga-Pentixafor, these patients might be good candidates for targeted radionuclide therapy with [177Lu]Lu-Pentixather in the future.

Liposomal Bupivacaine Suspension for Pain Control Following Ocular Evisceration Surgery.

PURPOSE: To determine the effectiveness of retrobulbar liposomal bupivacaine for controlling postoperative pain following evisceration, compared with 0.75% bupivacaine. METHODS: Randomized controlled trial, in which the postoperative pain scores from 24 patients who had retrobulbar liposomal bupivacaine after an evisceration were compared with the pain scores from 24 patients eviscerated using 0.75% bupivacaine. RESULTS: Patients who received liposomal bupivacaine reported significantly less pain at 24 hours (2.0 out of 10, p = 0.01) and 48 hours (2.2 out of 10, p = 0.01) after surgery than patients who received 0.75% bupivacaine (5.7, and 5.0, respectively). The postoperative pain scores at 1 hour and at 7 days did not significantly differ between the 2 groups. Significantly, fewer patients who received liposomal bupivacaine (0%) than patients who received 0.75% bupivacaine (16.7%) returned emergently during the postoperative period for uncontrolled pain (p ≤ 0.001). CONCLUSIONS: Retrobulbar liposomal bupivacaine is more effective than 0.75% bupivacaine for controlling pain during the first 2 days after evisceration and should be considered for patients undergoing this procedure.

Small Cell Neuroendocrine Carcinoma Presenting as Recurrent Dacryocystitis: Case Report of a Rare Entity.

An 84-year-old man presented with a localized, firm, tender mass over the right lacrimal sac. He had a history of acute dacryocystitis in the same eye 6 months before presentation, which resolved with antibiotics followed by uneventful dacryocystorhinostomy. At repeat presentation, the patient underwent orbital imaging and excisional biopsy of the lesion. Histologic studies revealed a small cell neuroendocrine carcinoma. The patient was subsequently treated with chemotherapy and radiation. Although there are rare reports of small cell neuroendocrine carcinoma originating in the sino-orbital-lacrimal region, this is the first report of tumor presentation with acute dacryocystitis in a patient with prior dacryocystorhinostomy.

Incidence, Risk Factors, and Management of Blindness after Orbital Surgery.

PURPOSE: Severe vision loss is a risk of orbital surgery which physicians should counsel patients about, but the overall risk rate is unknown. This research was conducted to determine the risk of severe vision loss related to orbital surgery. DESIGN: Retrospective review. PARTICIPANTS: Patients who underwent orbital surgery at either of 2 academic medical centers between January 1994 and December 2014. METHODS: A billing database search was conducted to identify all patients who had orbital surgery during the study period, cross-checked against diagnostic codes related to vision loss. Charts were screened to determine baseline demographic and medical history, surgical procedure, intraoperative and perioperative management, and visual acuity. Patients with preoperative visual acuity ≥20/200 that worsened ≤20/400 after orbital surgery were included for detailed review. Statistical analysis was conducted to identify factors posing particular risk or benefit to visual outcome in these patients. MAIN OUTCOME MEASURES: Visual acuity after orbital surgery. RESULTS: A total of 1665 patients underwent orbital surgery during the inclusion period, with 14 patients sustaining severe vision loss ranging from counting fingers at 1 foot to no light perception (overall risk, 0.84%). The causes of vision loss included retrobulbar hemorrhage, malpositioned implant, optic nerve ischemia, or direct optic nerve insult. When stratified by surgical approach, the risk of a blinding surgical complication was significantly higher for patients undergoing orbital floor repair in the setting of multiple facial fractures (subgroup risk, 6.45%), bony decompression of the optic canal (subgroup risk, 15.6%), or intracranial approach to the orbital roof (subgroup risk, 18.2%). Seven of 8 patients with a potentially reversible cause of postoperative vision loss underwent urgent repeat surgery, and 2 regained substantial vision (20/20 and 20/25). Administration of intravenous corticosteroids had no significant effect on visual acuity outcome. CONCLUSIONS: The overall risk of severe vision loss after orbital surgery is 0.84%. The subgroup risk is higher in patients undergoing facial polytrauma repair, optic canal decompression, or orbital apex surgery from an intracranial approach. Close postoperative monitoring and urgent assessment and management of acute vision loss may improve visual outcome in some patients.

Lateral Wall Orbital Decompression: Comparison of Outcomes in Rim Sparing and Temporary Rim Removal Techniques.

PURPOSE: To compare exophthalmos reduction in lateral orbital decompressions performed via rim sparing versus temporary rim removal techniques. METHODS: The authors performed a retrospective chart review of all patients who underwent simple lateral or combined medial and lateral wall orbital decompression between 2005 and 2013 by a single surgeon. Nineteen patients (33 orbits) were identified for inclusion in the study. Decompression procedures (1 or 2 orbital walls) involved either a rim sparing or a temporary rim removal technique. Preoperatively, all patients had stable exophthalmos defined as ≤1 mm change in exophthalmos over 2 consecutive visits. Measurements were taken again at the 3 to 4 months postoperative visit. Exclusion criteria were acute or unstable exophthalmos, exophthalmos secondary to malignancy, and patients lost to follow up. RESULTS: There were no significant differences in exophthalmos reduction for rim sparing versus temporary rim removal techniques in any of the groups studied. Simple lateral decompression procedures achieved 3.7 and 4.4 mm of exophthalmos reduction in rim sparing versus temporary rim removal techniques, respectively (P = 0.49). Exophthalmos reduction in combined medial and lateral wall orbital decompression was 4.1 mm for rim sparing and 3.5 mm for temporary rim removal techniques (P = 0.75). CONCLUSION: In our experience, orbital decompression approached through rim sparing or temporary rim removal techniques achieves similar results in simple lateral and combined medial and lateral decompressions. Though these techniques generate similar outcomes, temporary rim removal provides for improved visibility and access to deep orbital structures.

Carotid cavernous sinus fistulas without superior ophthalmic vein enlargement.

PURPOSE: Diagnosis of carotid cavernous fistula (CCF) relies on clinical findings, such as proptosis, chemosis, and pulsatile tinnitus, plus imaging features including enlargement of the superior ophthalmic vein (SOV). This study reviewed patients with CCF, with a focus on those who were clinically symptomatic but had a normal-appearing SOV on routine scans. METHODS: Retrospective review was conducted on the clinical records of patients with CCF seen by ophthalmology or interventional neuroradiology, with attention to clinical and imaging features, angiography findings, management, and outcomes. RESULTS: Forty patients presented with CCF. History of head trauma was present in 13 (average age 43.8 years; all direct or complex), while the remainder occurred spontaneously (average 66 years; 85% indirect). The most common presenting ophthalmologic signs or symptoms were proptosis (65%), binocular diplopia (60%), redness (57.5%), and chemosis (47.5%). After diagnosis, 36 underwent endovascular treatment, with successful occlusion achieved in 90% of cases for whom follow-up data was available (n = 21). Notably, 3 patients with CCF did not have SOV enlargement on any imaging modality including catheter angiography. CONCLUSIONS: In this series of patients with clinical signs of CCF, there was no radiologic evidence of enlarged SOV in 26% of patients on noninvasive imaging and in 8% on catheter angiography. To avoid inappropriate interventions or delays in diagnosis and care, it is important to recognize that CCF can exist without SOV enlargement. Patients with clinical features suspicious for CCF should undergo catheter angiography if treatment is being considered. Endovascular treatment can produce clinical improvement or resolution.

Neuro-ophthalmic deficits after head trauma.

Head trauma can injure the afferent and/or efferent visual systems, resulting in neuro-ophthalmic deficits. When assessing afferent pathway injuries, a stepwise approach to evaluating visual acuity, pupils, color perception, and visual fields is critical. Traumatic optic neuropathy is of especial importance and its management must be tailored on a case-by-case basis. Efferent pathway injuries should be assessed with attention to abnormalities of ocular alignment and motility, which may occur as isolated deficits or as part of a recognizable syndrome. Concussion or diffuse axonal injuries may also affect ophthalmologic function. Here, we review the extant literature describing the assessment and acute treatment of traumatic neuro-ophthalmic deficits.

Image quality and subject experience of quiet T1-weighted 7-T brain imaging using a silent gradient coil.

OBJECTIVES: Acoustic noise in magnetic resonance imaging (MRI) negatively impacts patients. We assessed a silent gradient coil switched at 20 kHz combined with a T1-weighted magnetisation prepared rapid gradient-echo (MPRAGE) sequence at 7 T. METHODS: Five healthy subjects (21-29 years; three females) without previous 7-T MRI experience underwent both a quiet MPRAGE (Q-MPRAGE) and conventional MPRAGE (C-MPRAGE) sequence twice. Image quality was assessed quantitatively, and qualitatively by two neuroradiologists. Sound level was measured objectively and rated subjectively on a 0 to 10 scale by all subjects immediately following each sequence and after the whole examination (delayed). All subjects also reported comfort level, overall experience and willingness to undergo the sequence again. RESULTS: Compared to C-MPRAGE, Q-MPRAGE showed higher signal-to-noise ratio (10%; p = 0.012) and lower contrast-to-noise ratio (20%; p < 0.001) as well as acceptable to good image quality. Q-MPRAGE produced 27 dB lower sound level (76 versus 103 dB). Subjects reported lower sound level for Q-MPRAGE both immediate (4.4 ± 1.4 versus 6.4 ± 1.3; p = 0.007) and delayed (4.6 ± 1.4 versus 6.3 ± 1.3; p = 0.005), while they rated comfort level (7.4 ± 1.0 versus 6.1 ± 1.7; p = 0.016) and overall experience (7.6 ± 1.0 versus 6.0 ± 0.9; p = 0.005) higher. Willingness to undergo the sequence again was also higher, however not significantly (8.1 ± 1.0 versus 7.2 ± 1.3; p = 0.066). CONCLUSION: Q-MPRAGE using a silent gradient coil reduced sound level by 27 dB compared to C-MPRAGE at 7 T while featuring acceptable-to-good image quality and a quieter and more pleasant subject experience.

Long-term follow-up of acquired nonaccommodative esotropia in a population-based cohort.

PURPOSE: To describe the clinical characteristics and long-term outcomes of children diagnosed over a 30-year period with acquired nonaccommodative esotropia (ANAET). DESIGN: Retrospective chart review of a population-based cohort. PARTICIPANTS: All pediatric (<19 years of age) residents of Olmsted County, Minnesota, who were diagnosed with ANAET from January 1, 1965, to December 31, 1994. METHODS: The medical records of all potential patients identified by the resources of the Rochester Epidemiology Project were reviewed. MAIN OUTCOME MEASURES: Incidence, clinical characteristics, and long-term motor and sensory outcomes of children with ANAET. RESULTS: A total of 174 children were diagnosed during the 30-year period, yielding an incidence of 1 in 287 live births. The median age at diagnosis for the 174 patients was 4.0 years (range, 10 months to 18.2 years), and 61% (107) were male (P = 0.009). Although 11% (8/75) of those queried were diplopic, none of the 174 was subsequently diagnosed with an intracranial lesion. During a mean follow-up of 10.9 years (range, 0 days to 37 years), 127 patients (73%) underwent strabismus surgery (mean, 1 surgery; range, 0-3 surgeries). Among the 127 patients who underwent surgery, the median final stereoacuity was 3000 seconds of arc, including 8 patients (6.3%) with ≥ 50 seconds of arc. Patients who were older (>44 months) at ANAET diagnosis (P = 0.005) and without amblyopia at their initial examination (P < 0.001) were more likely to achieve excellent final stereopsis. CONCLUSIONS: In this population-based cohort, ANAET occurred in 1 in 287 children and was more prevalent among male children. Although diplopia was relatively common, none of the children were found to have an intracranial malignancy. Most patients achieved good motor and sensory outcomes, with the best results among those with a later onset of their deviation and no amblyopia. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Lacrimal Gland Changes on Orbital Imaging after Glaucoma Drainage Implant Surgery.

PURPOSE: This study evaluates the radiographic appearance of lacrimal gland tissue after placement of a glaucoma drainage implant (GDI) to characterize the impact of the device on the gland's imaging patterns. METHODS: We performed retrospective chart review of departmental records at two urban academic medical centers, which were systematically searched using procedure codes to identify adult glaucoma patients who underwent unilateral superotemporal GDI from January 1995 to December 2015. Radiology records were cross-checked to identify the subset of patients who underwent postoperative orbital CT or MRI. Chart review collected data on glaucoma diagnosis, management, examination findings, and clinical complaints. Imaging studies were reviewed for orbital changes using qualitative assessment of the radiographic appearances and computer-guided calculations to quantify asymmetries. RESULTS: A review of all eye operations in the inclusion period identified 315 patients with GDI, 13 of whom were eligible for inclusion. Elapsed time from device placement to imaging averaged 41.9 months, and the average clinical follow-up was 56.4 months. Radiographic lacrimal gland changes were appreciable in 69% (9 of 13) of patients, most commonly with posterior displacement and flattening of the gland (7 of 13). ImageJ analysis revealed significantly smaller lacrimal glands in orbits with GDI (P = 0.04). No clear correlation was found between gland changes and clinical dry eye symptoms. CONCLUSION: GDI placement was associated with radiographically-appreciable lacrimal gland changes in two-thirds of patients, with changes occurring in a predictable pattern of lacrimal gland flattening, posteriorization, and volume loss. Radiographic changes correlated with clinical symptoms in few patients.

Divided eyelid nevus: a lid-sparing, staged surgical approach.

PURPOSE: To describe a method for staged partial resection of congenital divided eyelid nevus. The rationale, technique, and outcomes for this approach are described. DESIGN: Retrospective chart review of a case series. METHODS: Clinical records of 12 patients with divided eyelid nevus were reviewed with attention to presenting features, surgical management, histopathology, and follow-up course. Surgical approach involved the use of bipolar and thermal cautery to ablate the eyelid margin component, skin excision for cutaneous lesions, and then repair with advancement flaps or skin grafting. RESULTS: Eight patients with divided nevus were treated with a staged surgical approach: 5 primarily and 3 as revision cases. Average age was 16.3 years at primary presentation (range, 2-36 years), 16.5 years at initial surgery (range 2-36 years), and 36.0 years at presentation for revision (range, 12-72 years). Primary patients required 1 (n = 3) or 2 (n = 2) surgeries. Revision patients required 2 (n = 1) or 3 (n = 2) procedures in addition to those they had already undergone. Anterior lamellar repair was by granulation (n = 2), local skin flaps (n = 3), or skin grafts (n = 3). Average follow-up was 21.6 months (range, 0-98 months). No adverse effects or malignant transformations were seen. CONCLUSIONS: Patients with divided eyelid nevi often present for surgical management because of cosmetic and functional concerns. Because small-to-medium congenital nevi have a low risk of malignant transformation, total excision may not be necessary. A staged surgical approach with cautery ablation and contouring of the eyelid margin component and surgical resection of the anterior lamellar portion may be a reasonable treatment strategy for these patients.