Gregory C. Postel

Tumor Microenvironment–Dependent 18F-FDG, 18F-Fluorothymidine, and 18F-Misonidazole Uptake: A Pilot Study in Mouse Models of Human Non–Small Cell Lung Cancer

18F-FDG, 18F-fluorothymidine, and 18F-misonidazole PET scans have emerged as important clinical tools in the management of cancer; however, none of them have demonstrated conclusive superiority. The aim of this study was to compare the intratumoral accumulation of 18F-FDG, 18F-fluorothymidine, and 18F-misonidazole and relate this to specific components of the tumor microenvironment in mouse models of human non–small cell lung cancer (NSCLC). Methods: We used NSCLC A549 and HTB177 cells to generate subcutaneous and peritoneal xenografts in nude mice. Animals were coinjected with a PET radiotracer, pimonidazole (hypoxia marker), and bromodeoxyuridine (proliferation marker) intravenously 1 h before animal euthanasia. Tumor perfusion was assessed by Hoechst 33342 injection, given 1 min before sacrifice. The intratumoral distribution of PET radiotracers was visualized by digital autoradiography and related to microscopic visualization of proliferation, hypoxia, perfusion, stroma, and necrosis. Results: NSCLC xenografts had complex structures with intermingled regions of viable cancer cells, stroma, and necrosis. Cancer cells were either well oxygenated (staining negatively for pimonidazole) and highly proliferative (staining positively for bromodeoxyuridine) or hypoxic (pimonidazole-positive) and noncycling (little bromodeoxyuridine). Hypoxic cancer cells with a low proliferation rate had high18F-FDG and 18F-misonidazole uptake but low 18F-fluorothymidine accumulation. Well-oxygenated cancer cells with a high proliferation rate accumulated a high level of 18F-fluorothymidine but low 18F-FDG and18F-misonidazole. Tumor stroma and necrotic zones were always associated with low 18F-FDG, 18F-misonidazole, and 18F-fluorothymidine activity. Conclusion: In NSCLC A549 and HTB177 subcutaneously or intraperitoneally growing xenografts, 18F-fluorothymidine accumulates in well-oxygenated and proliferative cancer cells, whereas 18F-misonidazole and 18F-FDG accumulate mostly in poorly proliferative and hypoxic cancer cells. 18F-FDG and 18F-misonidazole display similar intratumoral distribution patterns, and both mutually exclude 18F-fluorothymidine.

Magnetic resonance imaging study of brain asymmetries in dyslexic patients.

Research studies suggest that the left hemisphere is involved in the pathophysiology of dyslexia. Thus far, the exact location and nature of the purported lesion(s) remain a matter of contention. The present study describes the distribution of structural abnormalities as related to brain symmetry in the brains of dyslexic individuals. High-resolution three-dimensional magnetic resonance images (MRIs) were analyzed in 16 dyslexic men and 14 controls matched for sex, age, educational level, and handedness. A computerized image analysis system was used to assess the volumetric deformations required to match each brain with its left-right mirror image. The results showed significant abnormalities in five left hemisphere structures involving the extrapyramidal and limbic systems: amygdala, hippocampus proper, parahippocampal gyrus, putamen, and globus pallidus. The left hemisphere is thought to play a major role in the temporal analysis of information. This stream of temporal analysis is of importance in motor movements. Reading might have evolved as an exaptation to motor movements requiring the sequential analysis of information. (J Child Neurol 2005;20:842—847).

Image annotation with Adobe Photoshop.

The authors relate the basic steps used to annotate grayscale cross sectional images with keyboard characters, arrowheads, and arrows using Adobe Photoshop 6.0 and 7.0.

The reverse Warburg effect and 18F-FDG uptake in non-small cell lung cancer A549 in mice: A pilot study

The purpose of this study was to observe the effect of fasting and feeding on 18F-FDG uptake in a mouse model of human non–small cell lung cancer. Methods: In in vivo studies, 18F-FDG small-animal PET scans were acquired in 5 mice bearing non–small cell lung cancer A549 xenografts on each flank with continuous feeding and after overnight fasting to observe the changes in intratumoral distribution of 18F-FDG and tumor 18F-FDG standardized uptake value (SUV). In ex vivo studies, intratumoral spatial 18F-FDG distribution assessed by autoradiography was compared with the tumor microenvironment (including hypoxia by pimonidazole and stroma by hematoxylin and eosin stain). Five overnight-fasted mice and 5 fed mice with A549 tumors were observed. Results: Small-animal PET scans were obtained in fed animals on day 1 and in the same animals after overnight fasting; the lapse was approximately 14 h. Blood glucose concentration after overnight fasting was not different from fed mice (P = 0.42), but body weight loss was significant after overnight fasting (P = 0.001). Intratumoral distribution of 18F-FDG was highly heterogeneous in all tumors examined, and change in spatial intratumoral distribution of 18F-FDG between 2 sets of PET images from the same mouse was remarkably different in all mice. Tumor 18F-FDG mean SUV and maximum SUV were not significantly different between fed and fasted animals (all P > 0.05, n = 10). Only tumor mean SUV weakly correlated with blood glucose concentration (R2 = 0.17, P = 0.03). In ex vivo studies, in fasted mice, there was spatial colocalization between high levels of 18F-FDG uptake and pimonidazole-binding hypoxic cancer cells; in contrast, pimonidazole-negative normoxic cancer cells and noncancerous stroma were associated with low 18F-FDG uptake. However, high 18F-FDG uptake was frequently observed in noncancerous stroma of tumors but rarely in viable cancer cells of the tumors in fed animals. Conclusion: Host dietary status may play a key role in intratumoral distribution of 18F-FDG. In the fed animals, 18F-FDG accumulated predominantly in noncancerous stroma in the tumors, that is, reverse Warburg effect. In contrast, in fasted status, 18F-FDG uptake was found in hypoxic cancer cells component (Pasteur effect). Our findings may provide a better understanding of competing cancer glucose metabolism hypotheses: the Warburg effect, reverse Warburg effect, and Pasteur effect.

Interhospital transfer of blunt multiply injured patients to a level 1 trauma center does not adversely affect outcome

BACKGROUND Stops at nontrauma centers for severely injured patients are thought to increase deaths and costs, potentially because of unnecessary imaging and indecisive/delayed care of traumatic brain injuries (TBIs). METHODS We studied 754 consecutive blunt trauma patients with an Injury Severity Score greater than 20 with an emphasis on 212 patients who received care at other sites en route to our level 1 trauma center. RESULTS Referred patients were older, more often women, and had more severe TBI (all P < .05). After correction for age, sex, and injury pattern, there was no difference in the type of TBI, Glasgow Coma Scale (GCS) upon arrival at the trauma center, or overall mortality between referred and directly admitted patients. GCS at the outside institution did not influence promptness of transfer. CONCLUSIONS Interhospital transfer does not affect the outcome of blunt trauma patients. However, the unnecessarily prolonged stay of low GCS patients in hospitals lacking neurosurgical care is inappropriate.

18F-Fluorodeoxyglucose Uptake and Tumor Hypoxia: Revisit 18F-Fluorodeoxyglucose in Oncology Application

This study revisited 18F-fluorodeoxyglucose (18F-FDG) uptake and its relationship to hypoxia in various tumor models. METHODS: We generated peritoneal carcinomatosis and subcutaneous xenografts of colorectal cancer HT29, breast cancer MDA-MB-231, and non–small cell lung cancer A549 cell lines in nude mice. The partial oxygen pressure (pO2) of ascites fluid was measured. 18F-FDG accumulation detected by digital autoradiography was related to tumor hypoxia visualized by pimonidazole binding and glucose transporter-1 (GLUT-1) in frozen tumor sections. RESULTS: Ascites pO2 was 0.90 ± 0.53 mm Hg. Single cancer cells and clusters suspended in ascites fluid as well as submillimeter serosal tumors stained positive for pimonidazole and GLUT-1 and had high 18F-FDG uptake. In contrast, 18F-FDG uptake was significantly lower in normoxic portion (little pimonidazole binding or GLUT-1 expression) of larger serosal tumors or subcutaneous xenografts, which was not statistically different from that in the liver. CONCLUSIONS: Glucose demand (18F-FDG uptake) in severely hypoxic ascites carcinomas and hypoxic portion of larger tumors is significantly higher than in normoxic cancer cells. Warburg effect originally obtained from Ehrlich ascites carcinoma may not apply to normoxic cancer cells. Our findings may benefit the better understanding of 18F-FDG PET in oncology application.

High signal on T1-weighted MR images of the head: A pictorial essay☆

T1-weighted magnetic resonance images (T1WI) of the head may manifest high signal in many normal and pathologic situations. Normally, it may be seen in fatty tissues, certain artifacts, and in areas without a blood-brain barrier after gadolinium administration. It is also seen in the posterior pituitary gland and in certain instances in the anterior pituitary gland. Pathologically, it may occur in many lesions after gadolinium enhancement, in fatty and cystic lesions, and in lesions with paramagnetic content. Occasionally, it may be seen in calcium deposition. Many of these are described and illustrated.

Software-Annotated, Digitally Photographed, and Printed MR Images: Suitability for Publication

RATIONALE AND OBJECTIVES The authors performed this study to evaluate whether digitally photographed, computer-annotated MR images produced by clinical radiologists and printed with an inexpensive photo printer are suitable for publication. MATERIALS AND METHODS Laser prints of 20 magnetic resonance images of the brain were photographed with a 3-megapixel digital camera and annotated with arrows, arrowheads, and asterisks by using graphics software that incorporates vector support. Then, 5 x 7-inch glossy prints with white borders were made by using an inexpensive photo printer. These prints were compared with those produced of the same 20 images by members of the medical centers graphics department with professional scanning and printing equipment and annotated with conventional rub-on symbols. Eight radiologists evaluated image and annotation quality and overall suitability for publication. RESULTS In all three categories, the images produced by radiologists outscored those produced by the graphics department. CONCLUSION Digitally photographed, software-annotated MR images printed with an inexpensive photo printer are suitable for publication.

SCROTAL HERNIATION OF THE BLADDER SECONDARY TO PROSTATE ENLARGEMENT

The roentgenographic findings of scrotal herniation of the bladder were first described by Levine in 1951.’ The term scrotal cystocele was used to describe the rare clinical condition of massive inguinoscrotal herniation of the bladder. Involvement of the bladder in inguinal hernias is not rare. However, herniation of a large portion of the bladder is uncommon. We report a case of massive inguinoscrotal herniation of the bladder secondary to large benign prostate hypertrophy. CASE REPORT A 78-year-old man presented with severe nocturia, a weak urinary stream, excessive straining and the need to squeeze the scrotum manually to void completely. Physical examination revealed a markedly enlarged prostate gland and a right inguinal hernia. Surgical history was significant for multiple repairs of the right inguinal hernia. Computerized tomography (CT) of the pelvis demonstrated a prostate gland measuring approximately 8 X 8 X 7 cm. (fig. 1, A). Subsequent images revealed the opacified bladder within the right inguinal canal, extending into the right hemiscrotum (fig. 1, B). Delayed supine images on excretory urography (Np) showed a large right inguinoscrotal herniation of the bladder with no evidence of ureteral displacement or dilatation (fig. 2). A simple retropubic prostatectomy revealed a 211 gm. benign prostate gland. The herniated portion of the bladder was reduced and elective hernioplasty was planned. DISCUSSION Herniation of the bladder may present as part of an obturator, ventral, ischiorectal, peritoneal or sciatic hernia. When the bladder is distended, it may also herniate into any pelvic or abdominal opening within its reach.2 Herniation of the bladder may be classified according to its relationship to the peritoneum. Paraperitoneal herniation is most common and is much more likely to be indirect. The bladder remains extraperitoneal being medial and alongside of the parietal