Lymphoma and Lactic Acidosis.

A 39-year-old man presented with new onset of sinus congestion, shortness of breath, and diaphoresis. His laboratory tests were notable for hypercalcemia and lactic acidosis. A CT scan of the head demonstrated mild paranasal disease. CT scan of the chest, abdomen, and pelvis demonstrated omental caking with lymphadenopathy and a thickened loop of bowel in the left upper quadrant suggestive of lymphoma. All abdominal lesions seen in the CT were intensely F-FDG avid with diffuse uptake in the bone marrow. There was markedly decreased F-FDG uptake in both the brain and liver. Histopathology was positive for Burkitt lymphoma.

Reference tissue normalization in longitudinal (18)F-florbetapir positron emission tomography of late mild cognitive impairment.

BACKGROUND: Semiquantitative methods such as the standardized uptake value ratio (SUVR) require normalization of the radiotracer activity to a reference tissue to monitor changes in the accumulation of amyloid-ß (Aß) plaques measured with positron emission tomography (PET). The objective of this study was to evaluate the effect of reference tissue normalization in a test-retest (18)F-florbetapir SUVR study using cerebellar gray matter, white matter (two different segmentation masks), brainstem, and corpus callosum as reference regions. METHODS: We calculated the correlation between (18)F-florbetapir PET and concurrent cerebrospinal fluid (CSF) Aß1-42 levels in a late mild cognitive impairment cohort with longitudinal PET and CSF data over the course of 2 years. In addition to conventional SUVR analysis using mean and median values of normalized brain radiotracer activity, we investigated a new image analysis technique-the weighted two-point correlation function (wS2)-to capture potentially more subtle changes in Aß-PET data. RESULTS: Compared with the SUVRs normalized to cerebellar gray matter, all cerebral-to-white matter normalization schemes resulted in a higher inverse correlation between PET and CSF Aß1-42, while the brainstem normalization gave the best results (high and most stable correlation). Compared with the SUVR mean and median values, the wS2 values were associated with the lowest coefficient of variation and highest inverse correlation to CSF Aß1-42 levels across all time points and reference regions, including the cerebellar gray matter. CONCLUSIONS: The selection of reference tissue for normalization and the choice of image analysis method can affect changes in cortical (18)F-florbetapir uptake in longitudinal studies.

Modeling clustered activity increase in amyloid-beta positron emission tomographic images with statistical descriptors.

BACKGROUND: Amyloid-beta (Aß) imaging with positron emission tomography (PET) holds promise for detecting the presence of Aß plaques in the cortical gray matter. Many image analyses focus on regional average measurements of tracer activity distribution; however, considerable additional information is available in the images. Metrics that describe the statistical properties of images, such as the two-point correlation function (S2), have found wide applications in astronomy and materials science. S2 provides a detailed characterization of spatial patterns in images typically referred to as clustering or flocculence. The objective of this study was to translate the two-point correlation method into Aß-PET of the human brain using 11C-Pittsburgh compound B (11C-PiB) to characterize longitudinal changes in the tracer distribution that may reflect changes in Aß plaque accumulation. METHODS: We modified the conventional S2 metric, which is primarily used for binary images and formulated a weighted two-point correlation function (wS2) to describe nonbinary, real-valued PET images with a single statistical function. Using serial 11C-PiB scans, we calculated wS2 functions from two-dimensional PET images of different cortical regions as well as three-dimensional data from the whole brain. The area under the wS2 functions was calculated and compared with the mean/median of the standardized uptake value ratio (SUVR). For three-dimensional data, we compared the area under the wS2 curves with the subjects' cerebrospinal fluid measures. RESULTS: Overall, the longitudinal changes in wS2 correlated with the increase in mean SUVR but showed lower variance. The whole brain results showed a higher inverse correlation between the cerebrospinal Aß and wS2 than between the cerebrospinal Aß and SUVR mean/median. We did not observe any confounding of wS2 by region size or injected dose. CONCLUSION: The wS2 detects subtle changes and provides additional information about the binding characteristics of radiotracers and Aß accumulation that are difficult to verify with mean SUVR alone.

Topical azithromycin therapy for meibomian gland dysfunction: clinical response and lipid alterations.

PURPOSE: Meibomian gland dysfunction (MGD) is a common clinical problem that is often associated with evaporative dry eye disease. Alterations of the lipids of the meibomian glands have been identified in several studies of MGD. This prospective, observational, open-label clinical trial documents the improvement in both clinical signs and symptoms of disease and spectroscopic behavior of the meibomian gland lipids after therapy with topical azithromycin ophthalmic solution. METHODS: Subjects with symptomatic MGD were recruited. Signs of MGD were evaluated with a slit lamp. Symptoms of MGD were measured by the response of subjects to a questionnaire. Meibum lipid, lipid-lipid interaction strength, and conformation and phase transition parameters were measured using Fourier transform infrared spectroscopy. RESULTS: In subjects with clinical evidence of MGD, changes in ordering of the lipids and resultant alteration of phase transition temperature were identified. Topical therapy with azithromycin relieved signs and symptoms and restored the lipid properties of the meibomian gland secretion toward normal. CONCLUSIONS: Improvement in phase transition temperature of the meibomian gland lipid with the determined percent trans rotomer composition of the lipid strongly suggests that the ordering of the lipid molecules is altered in the disease state (MGD) and that azithromycin can improve that abnormal condition toward normal in a manner that correlates with clinical response to therapy.