11C-MET PET/MRI for detection of recurrent glioma.

INTRODUCTION: Radiological assessment of brain tumors is widely based on the Radiology Assessment of Neuro-Oncology (RANO) criteria that consider non-specific T1 and T2 weighted images. Limitation of the RANO criteria is that they do not include metabolic imaging techniques that have been reported to be helpful to differentiate treatment related changes from true tumor progression. In the current study, we assessed if the combined use of MRI and PET with hybrid 11C-MET PET/MRI can improve diagnostic accuracy and diagnostic confidence of the readers to differentiate treatment related changes from true progression in recurrent glioma. METHODS: Fifty consecutive patients with histopathologically proven glioma were prospectively enrolled for a hybrid 11C-MET PET/MRI to differentiate recurrent glioma from treatment induced changes. Sole MRI data were analyzed based on RANO. Sole PET data and in a third evaluation hybrid 11C-MET-PET/MRI data were assessed for metabolic respectively metabolic and morphologic glioma recurrence. Diagnostic performance and diagnostic confidence of the reader were calculated for the different modalities, and the McNemar test and Mann-Whitney U Test were applied for statistical analysis. RESULTS: Hybrid 11C-MET PET/MRI was successfully performed in all 50 patients. Glioma recurrence was diagnosed in 35 of the 50 patients (70%). Sensitivity and specificity were calculated for MRI (86.11% and 71.43%), for 11C-MET PET (96.77% and 73.68%), and for hybrid 11C-MET-PET/MRI (97.14% and 93.33%). For diagnostic accuracy hybrid 11C-MET-PET/MRI (96%) showed significantly higher values than MRI alone (82%), whereas no significant difference was found for 11C-MET PET (88%). Furthermore, by rating on a five-point Likert scale significantly higher scores were found for diagnostic confidence when comparing 11C-MET PET/MRI (4.26 ± 0,777) to either PET alone (3.44 ± 0.705) or MRI alone (3.56 ± 0.733). CONCLUSION: This feasibility study showed that hybrid PET/MRI might strengthen RANO classification by adding metabolic information to conventional MRI information. Future studies should evaluate the clinical utility of the combined use of 11C-MET PET/MRI in larger patient cohorts.

Asymmetrical cranio-orbital facial stenosis.

Cranio-orbital facial scoliosis is the result of unilateral premature stenosis of the craniofacial skeleton. Plagiocephaly is only a subform of the syndrome. The deformity progresses unless operative treatment is given. Operative treatment is indicated for functional, aesthetic, and psychosocial reasons. We advocate early operation in infancy (3 to 6 months) consisting of wide resection of the stenosed sutures of the cranium and orbit, repositioning, and remodeling relying on the spontaneous autodynamic reshaping of the nasoethmoidal complex and the midface structures during the course of further growth. In adolescents and adults, multisegmental osteotomies and remodeling into a definitive position are necessary.

[Plastic surgery correction of combination craniofacial malformations. A survey for the obstetrician]. / Plastische Korrektur komplexer Schädel-Gesichtsmissbildungen. Eine Ubersicht für den Geburtshelfer.

Complex malformations of the skeleton of the cranium and face are mostly first discovered by the obstetrician. Almost all anomalies can be corrected already at infant age by means of update craniofacial surgery, provided they are diagnosed well in time and treatment is initiated directly. Surgery should be performed by a team that is well-versed in craniofacial surgery. A few examples are given to illustrate the most important malformations. Pointers to the best possible time of operation, indication and method are supplied.

Early operation in craniofacial dysostosis.

Craniofacial dysostosis is encountered in different congenital malformations such as Kleeblattschädel deformity, Crouzon's disease, and Apert's, Chotzen's, Pfeiffer's, and Carpenter's syndromes. Premature closure of cranial and facial sutures leads to characteristic disfigurement of the skull with orbital and maxillary hypoplasia. Operative treatment should be performed as early in life as possible to prevent further functional and esthetic deficiencies, and psychosocial problems. Correction is done by an intracranial approach with mobilization, remodeling, and advancement of the deformed skull. Thirty-two children have been operated during the first year of life with a maximum follow-up of 8 years. Most favorable results were obtained in 28 cases. The rate of complications were lower than in a series of children operated on later in life. We advocate that complex 1-stage corrections of craniofacial syndromes may be safely carried out during infancy utilizing modern techniques, expert pediatric anesthesia, and postoperative intensive care.

Heat evolution of cultured human keratinocytes.

The heat production of normal and transformed human epidermal keratinocytes precultured in Petriperm tissue culture dishes was measured calorimetrically. For this purpose, the membrane at the bottom of the culture dish was cut out aseptically and put into a microcalorimeter vessel with the cell layer inwards. A continuous heat output of (83 +/- 12) pW/cell was measured for normal keratinocytes from a confluent primary culture. A value of (134 +/- 35) pW/cell was obtained when the transformed keratinocyte line SV-K14 was used. The method described in this paper is simple, leads to reproducible results, and can be easily adapted to the calorimetric study of other mammalian cells in vitro.

Inactivation of Saccharomyces cells by 8-methoxypsoralen plus pulsed laser irradiation in the wavelength range 308 nm-380 nm.

Two different strains of Saccharomyces cerevisiae, one diploid wild type and one haploid mutant deficient in excision repair were irradiated with laser pulses in the range 308 nm to 380 nm after 8-MOP treatment. Both the shoulder (Dq) and the final slope (Do) of the inactivation curves were dependent on wavelength which showed a broad minimum around 355 nm. No differences in inactivation were recorded after pulsed irradiations between the repetition rates of 5 Hz and 35 Hz. Irradiations with pulses of the energy density from 0.1 mJ/cm2 up to 26 mJ/cm2 resulted in a final slope increasing with pulse energy density. This was in contrast to the effects of irradiation alone.

Microcalorimetric investigations of the metabolism of yeasts. VII. Flow-calorimetry of aerobic batch cultures.

The heat evolution of aerobic batch cultures of growing yeast (Saccharomyces cerevisiae) in glucose media was investigated by a combination of a flow-microcalorimeter with a fermentor vessel. The course of heat production, cell production and the rate of oxygen consumption were qualitatively the same for all glucose concentrations between 10 mM and 100 mM. Under optimal aerobic conditions a triphasic growth was observed due to the fermentation of glucose to ethanol, respiration of ethanol to CO2 and acetate, and respiration of acetate to CO2. Energy and carbon were found to be in balance for all glucose concentrations.

Minimum phototoxicity dose (MPD). Comparison of conventional light sources and different lasers.

A pilot study was performed on groups of 5-7 volunteers to evaluate the minimum phototoxicity dose (MPD) of several light sources with different UVA qualities to optimise photochemotherapy. Visual observation was more suitable than reflection photometry in determining the threshold and gradation of erythema reactions; thermometry gave poor results. There were no individual differences between the MPD of a PUVA 4000 box and a continuously emitting argon-ion laser with 40 and 400 mW, respectively. The pulsed radiation of a nitrogen laser was the most effective. The limited validity of the Bunsen-Roscoe law for high peak power could thus be tested for a secondary photochemical reaction of the skin. The nitrogen laser (337.1 nm) proved that a repetition rate of 20 Hz was superior to 10 and 40 Hz. The MPD was intraindividually higher at 25 Hz than at 10 and 16.7 Hz for the dye laser tested (325 and 330 nm, respectively).

Microcalorimetric investigations of the metabolism of isolated human epidermis.

Microcalorimetry was used for the evaluation of metabolic and enzyme activity in human epidermis. The endogenous metabolism with a heat production Q = -2 muW/mg wet weight could be stimulated to Q = -12 muW/mg by adding glucose to the buffer. To test the enzyme activity, hydrogenation of pyruvate to lactate by lactate dehydrogenase (LDH) was chosen as an essential step of anaerobic glycolysis. The LDH activity of epidermis slices amounted to 22 mU/mg epidermis. The microcalorimetric method is discussed as a test procedure for specimens of healthy and diseased skin and for cell cultures.

Microcalorimetric investigations of the metabolism of yeasts. VI. Diauxy during anaerobic growth on different saccharides.

The anaerobic growth of the yeast Saccharomyces cerevisiae with six different mono- and disaccharides as energy source was investigated calorimetrically. With mixtures of monosaccharides and disaccharides or disaccharides with each other, biphasic thermograms were obtained. The diauxic growth is discussed in view of constitutive and inducible transport systems and degradation enzymes.

Calorimetric characterization of microorganisms.

A short survey is given on recent calorimetric studies of microbial growth, which raised the question whether calorimetrically obtained thermograms can be used for identification of different organisms. Advantages and the efficiency of the method are critically discussed.

Microcalorimetric investigation of the metabolism of yeasts. V. Influence of ploidy on growth and metabolism.

Microcalorimetric experiments on growth and maintenance metabolism of Saccharomyces strains ranging from haploid to hexaploid are described. During growth, the mean dry weight, the mean volume and the maximum heat flux of the cells are nearly linear functions of ploidy. These parameters are correlated with the cell concentration in such a manner that the weight-specific heat production and the grown biomass are independent of ploidy. For the metabolism of maintenance, two levels of the specific heat flux are found, the lower of which is occupied by the haploids, diploids and triploids. The higher polyploids exhibit the higher level.

Experimental investigation of the bound dissipation function: change of the psi u-function during the growth of yeast.

By means of a microcalorimeter (direct calorimetry) and a Warburg-apparatus (indirect calorimetry) that part of the dissipation of a growing culture of yeast cells which remains irreversible in the cells is determined (psi u). The course of the psi u-function with time correlates with the increase of the specific cell concentration being conditioned by the growth phase of the culture but similar for fermentative and respirative metabolism.