Accuracy and self-validation of automated bone age determination.

The BoneXpert method for automated determination of bone age from hand X-rays was introduced in 2009 and is currently running in over 200 hospitals. The aim of this work is to present version 3 of the method and validate its accuracy and self-validation mechanism that automatically rejects an image if it is at risk of being analysed incorrectly. The training set included 14,036 images from the 2017 Radiological Society of North America (RSNA) Bone Age Challenge, 1642 images of normal Dutch and Californian children, and 8250 images from Tübingen from patients with Short Stature, Congenital Adrenal Hyperplasia and Precocious Puberty. The study resulted in a cross-validated root mean square (RMS) error in the Tübingen images of 0.62 y, compared to 0.72 y in the previous version. The RMS error on the RSNA test set of 200 images was 0.45 y relative to the average of six manual ratings. The self-validation mechanism rejected 0.4% of the RSNA images. 121 outliers among the self-validated images of the Tübingen study were rerated, resulting in 6 cases where BoneXpert deviated more than 1.5 years from the average of the three re-ratings, compared to 72 such cases for the original manual ratings. The accuracy of BoneXpert is clearly better than the accuracy of a single manual rating. The self-validation mechanism rejected very few images, typically with abnormal anatomy, and among the accepted images, there were 12 times fewer severe bone age errors than in manual ratings, suggesting that BoneXpert could be safer than manual rating.

Personal perception and body awareness of dysmenorrhea and the effects of rhythmical massage therapy and heart rate variability biofeedback-A qualitative study in the context of a randomized controlled trail.

OBJECTIVE: The purpose was to involve women's personal experiences of daily life with primary dysmenorrhea (PD) and their body perceptions of the dysmenorrhea-related symptoms in relation to the treatment procedure and to explore the perception of Heart Rate Variability Biofeedback (HRV-BF) or Rhythmical Massage (RM) according to Ita Wegman as a therapeutic intervention within the framework of Anthroposophic Medicine (AM). DESIGN: From 60 women who participated in our randomized controlled trial analyzing the effects of HRV-BF or RM, we examined 14 women to get an in-depth understanding of this prevalent disease, using a qualitative design. The women drew their body image before and after the 3-month-intervention on body silhouette diagrams and described their body-perceptions. Semi-structured interviews were conducted and analyzed using content analysis. RESULTS: Women perceive dysmenorrhea as a disturbance of their daily lives. The body images showed the variations of experience, from misbalances of body perception to overwhelming attacks of pain hindering a normal life for several days per month. Perception of therapeutic interventions range from relaxing without effects on complaints to important changes and benefits on the physical, emotional, and/or social level. Both therapies can support stronger self-awareness through enabling a more differentiated sense of body-awareness, sometimes resulting in women experiencing fewer limitations in their daily lives. Effects may be influenced by the readiness to resonate with the therapeutic process. Qualitative interviews and body images can serve as tools to integrate individuality and help to integrate embodied more or less conscious aspects of complaints. CONCLUSIONS: The body silhouette diagram could be used systematically to include reflections of embodiment in the therapeutic and research settings and help to diagnose in advance the ability of participants to resonate with interventions. RM and HRV-BF influence self-awareness and may enable salutogenic and self-management capacities. For more effective treatment it may be helpful to make treatment suggestions based on an integrative individual history that includes preferences, expectations and a body silhouette diagram.

A human huntingtin SNP alters post-translational modification and pathogenic proteolysis of the protein causing Huntington disease.

Post-translational modifications (PTMs) are key modulators of protein function. Huntington disease (HD) is a dominantly inherited neurodegenerative disorder caused by an expanded CAG trinucleotide repeat in the huntingtin (HTT) gene. A spectrum of PTMs have been shown to modify the normal functions of HTT, including proteolysis, phosphorylation and lipidation, but the full contribution of these PTMs to the molecular pathogenesis of HD remains unclear. In this study, we examine all commonly occurring missense mutations in HTT to identify potential human modifiers of HTT PTMs relevant to HD biology. We reveal a SNP that modifies post-translational myristoylation of HTT, resulting in downstream alterations to toxic HTT proteolysis in human cells. This is the first SNP shown to functionally modify a PTM in HD and the first validated genetic modifier of post-translational myristoylation. This SNP is a high-priority candidate modifier of HD phenotypes and may illuminate HD biology in human studies.

Mechanography in childhood: references for force and power in counter movement jumps and chair rising tests.

OBJECTIVE: We sought to procure age- and gender- related reference data and study the characteristics of body weight related peak force (pFrel), body mass related peak power (pPrel) for counter movement jumps (single two-legged jumps, s2LJ) and chair rising tests (CRT) in children. METHODS: We examined 868 healthy participants (436 female) aged 3 to 19 years. Weight-related results of the s2LJ and CRT Mechanography parameters were reported. RESULTS: pPrel during s2LJ (pPrel(s2LJ)) increased linearly with age for males age 5 to 19 and female age 5 to 11 at a rate of 4.6 W/kg per year. pPrel(s2LJ) for females age 12 to 19 increased only by 2.5 W/kg. CRT time per repetition was 1.065 s, independent of age and gender. pPrel per body mass during the rise phase (pPrel(CRT)) showed similar but smaller age and gender relations as peak power during s2LJ. pFrel was 2.5 g (multiples of earth's gravity) for s2LJ and 1.5 g for CRT. CONCLUSION: This data from normal children from a healthy Caucasian population provide reference values for tests that reflect everyday motor function.

Mechanography in childhood: references for grip force, multiple one-leg hopping force and whole body stiffness.

OBJECTIVE: We sought to study and procure reference values for weight-related maximum isometric grip force (MIGF), maximum voluntary force in relation to body weight (Fmvrel) and peak whole body stiffness (pKwb) in multiple one-legged hopping (m1LH) in childhood. METHODS: We examined 868 children and adolescents (436 female) aged 3 to 19 yrs. Weight related results are reported as multiples of earth's gravity (g). RESULTS: MIFG and Fmv(m1LH) are highly linearly correlated with body weight. After adjustment for weight, mean Fmvrel(m1LH) increases from the age of 3 to 6 yrs, then remains at 3.33 g (SD 0.31 g) between 6 and 19 yrs, independent of age and gender. The difference between legs decreases from 10% at 3 yrs to a constant 5.5% after the age of 7 yrs. Weight-adjusted MIGF also increases steeply from 3 to 6 yrs, then shows a further linear, less steep increase - in males through to age 19 yrs while females show a near-standstill after the age of 12 yrs. pKwb(m1LH) increases from the age of 7 yrs. CONCLUSION: This data from normal children from a healthy Caucasian population provide a reference for tests of motor function.

Diversity in auxology: between theory and practice. Proceedings of the 18th Aschauer Soiree, 13th November 2010.

Auxology has developed from mere describing child and adolescent growth into a vivid and interdisciplinary research area encompassing human biologists, physicians, social scientists, economists and biostatisticians. The meeting illustrated the diversity in auxology, with the various social, medical, biological and biostatistical aspects in studies on child growth and development.

Short children with low birth weight born either small for gestational age or average for gestational age show similar growth response and changes in insulin-like growth factor-1 to growth hormone treatment during the first prepubertal year.

BACKGROUND/AIMS: Growth hormone (GH) is an accepted treatment for short children born small for gestational age (SGA). The aim of this analysis was to compare the growth response to GH in children with low birth weight born SGA or appropriate for gestational age (AGA). METHODS: This retrospective observational study is from one center. Of all the children with a birth weight <2,500 g treated, 50 were primarily diagnosed as having growth hormone deficiency ([A] SGA, n = 26; [B] AGA, n = 24) and 138 were originally diagnosed SGA or AGA (reclassified: [C] SGA, n = 102; [D] AGA, n = 36). RESULTS: [Median; A, B, C, D]: at an age of 4.9, 5.2, 5.8, 5.8 years, a height of -2.9, -2.4, -2.8, -2.9 SDS and a GH dose of 27, 28, 41, 39 µg/kg/day, the children grew 0.9, 0.9, 0.8, 0.9 SDS in height, respectively. Insulin-like growth factor-1 (IGF-1) at GH start was, respectively, -2.1, -2.2, -0.4, -0.9 SDS and rose to (delta IGF-1) 1.8, 2.0, 1.7, 1.5 SDS during the first year on GH. All differences were not significant. CONCLUSIONS: We show for the first time that short stature children with low birth weight born AGA experience the same increase in height and IGFs to GH treatment as those born SGA irrespective of actual GH secretory status.

Metacarpal thickness, width, length and medullary diameter in children--reference curves from the First Zürich Longitudinal Study.

SUMMARY: Metacarpal thickness (T), width (W), length (L) and medullary diameter (M) were measured in 3,121 X-rays from 231 healthy Caucasian children aged 3 to 19 years and analysed for bone age, age, height, weight and gender-related characteristics, showing highly differentiated growth patterns with prepubertal dips. Reference data for the four metacarpal measures are presented. INTRODUCTION: The aim of the study was to create and explore a reference database for metacarpal T, W, L and M in children. METHODS: Three thousand one hundred twenty-one left-hand X-rays (1,661 from boys) from 231 healthy Caucasian subjects (119 boys) aged 3 to 19 years were analysed by BoneXpert, a programme for automatic analysis of hand X-rays and bone age (BA; in years). RESULTS: In boys, growth of T, W and L shows a prepubertal decrease from BA 7 to 13 and then accelerates again. In girls, the same is seen only for T starting from BA 8 to 11, whereas W and L grow at a declining rate. M shows steady growth until BA 10.5 in girls and BA 13.5 in boys and then grows smaller in both. W is greater in boys from BA 6 onwards, while L is greater in girls from BA 9 to 13 and T from BA 11 to 14. BA is reflected best by L until start of puberty and by T and L thereafter. CONCLUSION: T, W, L and M show highly differentiated growth patterns. These reference data provide a basis for further research into skeletal development and the management of hormone therapies in children.

A paediatric bone index derived by automated radiogrammetry.

SUMMARY: Hand radiographs are obtained routinely to determine bone age of children. This paper presents a method that determines a Paediatric Bone Index automatically from such radiographs. The Paediatric Bone Index is designed to have minimal relative standard deviation (7.5%), and the precision is determined to be 1.42%. INTRODUCTION: We present a computerised method to determine bone mass of children based on hand radiographs, including a reference database for normal Caucasian children. METHODS: Normal Danish subjects (1,867), of ages 7-17, and 531 normal Dutch subjects of ages 5-19 were included. Historically, three different indices of bone mass have been used in radiogrammetry all based on A = piTW(1 - T/W), where T is the cortical thickness and W the bone width. The indices are the metacarpal index A/W(2), DXR-BMD = A/W, and Exton-Smith's index A/(WL), where L is the length of the bone. These indices are compared with new indices of the form A/(W(a) L(b)), and it is argued that the preferred index has minimal SD relative to the mean value at each bone age and sex. Finally, longitudinal series of X-rays of 20 Japanese children are used to derive the precision of the measurements. RESULTS: The preferred index is A/(W(1.33) L(0.33)), which is named the Paediatric Bone Index, PBI. It has mean relative SD 7.5% and precision 1.42%. CONCLUSIONS: As part of the BoneXpert method for automated bone age determination, our method facilitates retrospective research studies involving validation of the proposed index against fracture incidence and adult bone mineral density.

The course of neonatal cholestasis in congenital combined pituitary hormone deficiency.

BACKGROUND: Neonatal cholestatic hepatitis is frequently associated with congenital combined pituitary hormone deficiency (CCPHD). Data on the course of this hepatopathy are scarce. AIM: We retrospectively analyzed the data of all CCPHD infants with cholestasis who presented at the University Children's Hospital, Tuebingen. RESULTS: All infants (n = 9; 2 females) presented with early and prolonged jaundice, failure to thrive and recurrent hypoglycemia. All males had micropenis and 3/7 cryptorchidism. Median age at diagnosis was 1.4 months. Cholestasis began at a median age of 13 days (range 5-31) and resolved at 88 days (54-174). Maximum direct bilirubin level was 6.9 mg/dl (2.4-11.6). Peaks of ALP (median 721 U/l), ALT (148 U/l) and AST (195 U/l) occurred 2-4 weeks later, while GGT levels were elevated in only two infants (167 U/l). Functional liver parameters were always normal. Liver biopsies (n = 4) showed canalicular cholestasis and mild portal eosinophilic infiltration. TEBIDA radioisotope excretion into the intestinal tract was blocked. Substitution with Lthyroxine, hydrocortisone and growth hormone seemed to accelerate the cure from cholestasis. Liver function at follow-up (median 4 yr) stayed normal. CONCLUSION: Cholestasis in CCPHD follows the course described here, frequently with normal GGT levels.

Cortical bone density is normal in prepubertal children with growth hormone (GH) deficiency, but initially decreases during GH replacement due to early bone remodeling.

Dual energy x-ray absorptiometry (DEXA) has revealed that GH- deficient adults gain in bone mineral density during GH therapy. Measurements of volumetric bone density (grams per cubic centimeter vs. grams per square centimeter) and structure, however, are achieved through peripheral quantitative computed tomography (pQCT). In 45 prepubertal GH-deficient children, we studied pQCT measurements before the start and for 12 months of GH treatment. Serum alkaline phosphatase (AP), procollagen I carboxyl-terminal propeptide (PICP), and deoxypyridinoline reflected bone metabolism status. Findings at the start of GH treatment were (mean SD score): bone area, -0.44; cortical density, -0.03; cortical area, -1.32; cortical thickness, -1.41; and marrow area, +0.66. At 12 months, cortical density had fallen to -0.73 (P < 0.001), whereas cortical area and thickness, and marrow area did not change. AP, PICP, and deoxypyridinoline increased significantly within the first 3 months (increase: AP, 66.5 U/liter; PICP, 72 microg/liter; DPD, 11.4 nmol/mmol creatinine). The pQCT showed that cortical density is not reduced in GH-deficient patients. Higher bone metabolism explains the lower cortical density after GH therapy commenced. Thus, the manifestation of GH deficiency is evidently similar in children and adults, and pQCT provides important information in addition to DEXA measurements, as DEXA does not take bone structure into account.

Characterization of a naturally occurring trans-splicing intein from Synechocystis sp. PCC6803.

A naturally occurring trans-splicing intein from the dnaE gene of Synechocystis sp. PCC6803 (Ssp DnaE intein) was used to characterize the intein-catalyzed splicing reaction. Trans-splicing/cleavage reactions were initiated by combining the N-terminal splicing domain of the Ssp DnaE intein containing five native N-extein residues and maltose binding protein as the N-extein with the C-terminal Ssp DnaE intein splicing domain (E(C)) with or without thioredoxin fused in-frame to its carboxy terminus. Observed rate constants (k(obs)) for dithiothreitol-induced N-terminal cleavage, C-terminal cleavage, and trans-splicing were (1.0 +/- 0.5) x 10(-3), (1.9 +/- 0.9) x 10(-4), and (6.6 +/- 1.3) x 10(-5) s(-1), respectively. Preincubation of the intein fragments showed no change in k(obs), indicating association of the two splicing domains is rapid relative to the subsequent steps. Interestingly, when E(C) concentrations were substoichiometric with respect to the N-terminal splicing domain, the levels of N-terminal cleavage were equivalent to the amount of E(C), even over a 24 h period. Activation energies for N-terminal cleavage and trans-splicing were determined by Arrhenius plots to be 12.5 and 8.9 kcal/mol, respectively. Trans-splicing occurred maximally at pH 7.0, while a slight increase in the extent of N-terminal cleavage was observed at higher pH values. This work describes an in-depth kinetic analysis of the splicing and cleavage activity of an intein, and provides insight for the use of the split intein as an affinity domain.

Switching osmolyte strategies: response of Methanococcus thermolithotrophicus to changes in external NaCl.

Methanococcus thermolithotrophicus, a thermophilic methanogenic archaeon, produces and accumulates beta-glutamate and L-alpha-glutamate as osmolytes when grown in media with <1 M NaCl. When the organism is adapted to grow in >1 M NaCl, a new zwitterionic solute, N(epsilon)-acetyl-beta-lysine, is synthesized and becomes the dominant osmolyte. Several techniques, including in vivo and in vitro NMR spectroscopy, HPLC analyses of ethanol extracts, and potassium atomic absorption, have been used to monitor the immediate response of M. thermolithotrophicus to osmotic stress. There is a temporal hierarchy in the response of intracellular osmolytes. Changes in intracellular K(+) occur within the first few minutes of altering the external NaCl. Upon hypoosmotic shock, K(+) is released from the cell; relatively small changes occur in the organic osmolyte pool on a longer time scale. Upon hyperosmotic shock, M. thermolithotrophicus immediately internalizes K(+), far more than would be needed stoichiometrically to balance the new salt concentration. This is followed by a decrease to a new K(+) concentration (over 10-15 min), at which point synthesis and accumulation of primarily L-alpha-glutamate occur. Once growth of the M. thermolithotrophicus culture begins, typically 30-100 min after the hyperosmotic shock, the intracellular levels of organic anions decrease and the zwitterion (N(epsilon)-acetyl-beta-lysine) begins to represent a larger fraction of the intracellular pool. The observation that N(epsilon)-acetyl-beta-lysine accumulation occurs in osmoadapted cells but not immediately after osmotic shock is consistent with the hypothesis that lysine 2,3-aminomutase, an enzyme involved in N(epsilon)-acetyl-beta-lysine synthesis, is either not present at high levels or has low activity in cells grown and adapted to lower NaCl. That lysine aminomutase specific activity is 8-fold lower in protein extracts from cells adapted to low NaCl compared to those adapted to 1.4 M NaCl supports this hypothesis.

Platelet cyclic GMP responses to nitroglycerin.

The present study further investigates the use of platelet cyclic guanosine monophosphate (GMP) as a biochemical measure of tolerance. Platelet cyclic GMP has been reported as a marker of the biochemical effects of nitroglycerin (GTN) and as an indicator of the development of tolerance. Platelet cyclic GMP levels and systolic blood pressure (SBP) were measured repeatedly in nine subjects who received continuous transdermal GTN therapy (0.6 mg/hour), and in nine control subjects who did not. These measurements were also made before and after sublingual GTN (0.6 mg) in both groups. Whole blood from five subjects was incubated with normal saline (as a control), with 22 nM GTN (representing a therapeutic GTN concentration), and with 100 microM GTN. Although the acute administration of transdermal GTN caused a significant decrease in SBP (112 +/- 3 to 96 +/- 3 mmHg, p = 0.003), SBP returned to baseline following 1 week of continuous therapy. Platelet cyclic GMP levels did not change in response to transdermal GTN, either acutely or following sustained therapy. Similarly, sublingual GTN caused no change in platelet cyclic GMP in either group. There was no change in platelet cyclic GMP concentration following incubation with 22 nM GTN. Platelet cyclic GMP did increase following incubation with 100 microM GTN (0.883 +/- 0.043 pmol/10(9) platelets, p < 0.001). These results demonstrate that platelet cyclic GMP levels do not change in response to clinically relevant doses of GTN. Literature supporting the use of platelet cyclic GMP levels as an index of GTN effects and/or tolerance should be interpreted with caution.

Complications of balloon catheterization associated with aberrant cerebral arterial anatomy in a horse with guttural pouch mycosis.

A 3-year-old Quarter Horse gelding was treated for left guttural pouch mycosis by ligation and balloon catheterization of the left internal carotid artery. Catheter advancement was shorter (10 cm) than the normally reported distance (13-15 cm), but was observed endoscopically during placement as it coursed within the internal carotid artery through the guttural pouch. The horse developed a persistently abnormal respiratory pattern after catheter placement, failed to gain consciousness, developed pulmonary edema, and died 5.5 hours postoperatively. Postmortem examination revealed an aberrant left internal carotid arterial course with location of the embolectomy catheter at the junction of the basilar and caudal cerebellar arteries. Brainstem neuronal necrosis and alveolar and interstitial pulmonary edema were identified on histological examination. Angiography may be used to identify aberrant branching patterns. Failure to identify and occlude aberrant branches may result in fatal epistaxis and Brainstem lesions.

Effects of intramuscular sedative and opioid combinations on tear production in dogs.

The effect of commonly used sedation protocols on tear production rate was evaluated in dogs. Schirmer I tear tests were examined before and after intramuscular injection of acepromazine and oxymorphone (ACE + OXY; n = 7), diazepam and butorphanol (DIA + BUT; n = 8), and xylazine and butorphanol (XYL + BUT; n = 8). Two Schirmer I tear tests were also performed 15-25 min apart in dogs which received no sedative drugs (control; n = 4). Tear production rate decreased to 15 +/- 2, 17 +/- 1, and 6 +/- 1 mm min-1, respectively, while control animals averaged 21 +/- 2 mm min-1 at the same time point. Because XYL + BUT profoundly decreased tear production rate, we evaluated the two drugs separately. While BUT mildly decreased tear production when given alone to dogs (18 +/- 1 mm min-1; n = 5), xylazine had no effect on tear production. Thus it appears that the two agents act synergistically to decrease tear production rate in dogs. Moreover, sterile ocular lubricant or tear replacement should be used during XYL + BUT sedation.

Hemodynamic effects of epidural ketamine in isoflurane-anesthetized dogs.

OBJECTIVE: The purpose of this study was to determine the hemodynamic effects of epidural ketamine administered during isoflurane anesthesia in dogs. STUDY DESIGN: Prospective, single-dose trial. ANIMALS: Six healthy dogs (five males, one female) weighing 25.3 +/- 3.88 kg. METHODS: Once anesthesia was induced, dogs were maintained at 1.5 times the predetermined, individual minimum alveolar concentration (MAC) of isoflurane. Dogs were instrumented and allowed to stabilize for 30 minutes before baseline measurements were recorded. Injection of 2 mg/kg of ketamine in 1 mL saline/4.5 kg body weight was then performed at the lumbosacral epidural space. Hemodynamic data were recorded at 5, 10, 15, 20, 30, 45, 60, and 75 minutes after epidural ketamine injection. Statistical analysis included an analysis of variance (ANOVA) for repeated measures over time. All data were compared with baseline values. A P < .05 was considered significant. RESULTS: Baseline values +/- standard error of the mean (X +/- SEM) for heart rate, mean arterial pressure, mean pulmonary artery pressure, central venous pressure, pulmonary capillary wedge pressure, cardiac index, stroke index, systemic vascular resistance, pulmonary vascular resistance, and rate-pressure product were 108 +/- 6 beats/min, 85 +/- 10 mm Hg, 10 +/- 2 mm Hg, 3 +/- 1 mm Hg, 5 +/- 2 mm Hg, 2.3 +/- 0.3 L/min/m2, 21.4 +/- 1.9 mL/beat/m2, 3386 +/- 350 dynes/sec/cm5, 240 +/- 37 dynes/sec/cm5, and 12376 +/- 1988 beats/min x mm Hg. No significant differences were detected from baseline values at any time after ketamine injection. CONCLUSIONS: The epidural injection of 2 mg/kg of ketamine is associated with minimal hemodynamic effects during isoflurane anesthesia. CLINICAL RELEVANCE: These results suggest that if epidural ketamine is used for analgesia in dogs, it will induce minimal changes in cardiovascular function.

Treatment of rupture of suspensory ligament and superficial flexor tendon in a bull.

Rupture of the suspensory ligament at the insertions on the proximal sesamoid bones, and of the superficial flexor tendon of the left fore limb, occurred in an adult Angus bull as a result of fighting. There was severe hyperextension of the metacarpophalangeal (MCP) joint with the dewclaws almost touching the ground. Radiographs revealed severe hyperextension of the MCP joint with the sesamoid bones aligned directly distal to the metacarpus. Initially, a full length fiberglass cast was applied with the limb partially flexed within the cast and the heels elevated. The cast was replaced twice. The cast was removed after 136 days and the bull was bearing full weight on the limb. Prolonged immobilisation of the limb produced new bone in the area (a normal response in cattle) to cause ankylosis of the traumatized MCP joint and partial ankylosis of the carpus. The bull was being used for pasture breeding one year after the injury.

The fatty acid composition of human gliomas differs from that found in nonmalignant brain tissue.

To compare the fatty acid composition of tumor tissue from glioma patients with that of normal brain tissue, tissue samples were obtained from 13 glioma patients and from 3 nonmalignant patients. Following lipid extraction, total fatty acid composition was measured using gas-liquid chromatography. samples were further separated into phospholipids and neutral lipids. Representative samples were then separated into phospholipid classes by thin-layer chromatography and the fatty acid composition assayed. Levels of the polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA), were significantly reduced (P = 0.029) in the glioma samples compared with normal brain samples; mean values were 4.8 +/- 2.9% and 9.2 +/- 1.0%, respectively. This reduction in glioma DHA content was also observed in terms of phospholipids (4.6 +/- 2.1% vs. 9.6 +/- 0.8%, P = 0.002). The phosphatidylserine and phosphatidylethanolamine phospholipid classes were reduced in the glioma samples. Differences were also noted in the n-6 PUFA content between glioma and normal brain samples. The glioma content of the n-6 PUFA linoleic acid was significantly greater (P < 0.05) than that observed in the control samples in terms of total lipids. Thus, the fatty acid composition of human gliomas differs from that found in nonmalignant brain tissue.

Tumor perfusion studies using fast magnetic resonance imaging technique in advanced cervical cancer: a new noninvasive predictive assay.

PURPOSE: This study investigated sequential changes in tumor blood supply using magnetic resonance (MR) perfusion imaging and assessed their significance in the prediction of outcome of patients with advanced cervical cancer. The purpose of this project was to devise a simple, noninvasive method to predict early signs of treatment failure in advanced cervical cancer treated with conventional radiation therapy. METHODS AND MATERIALS: Sixty-eight MR perfusion studies were performed prospectively in 17 patients with squamous carcinomas (14) and adenocarcinomas (3) of the cervix, Stages bulky IB (1), IIB (5), IIIA (1), IIIB (8), and IVA (1), and recurrent (1). Four sequential studies were obtained in each patient: immediately before radiation therapy (pretherapy), after a dose of 20-22 Gy/ approximately 2 weeks (early therapy), after a dose of 40-45 Gy/ approximately 4-5 weeks (midtherapy), and 4-6 weeks after completion of therapy (follow-up). Perfusion imaging of the tumor was obtained at 3-s intervals in the sagittal plane. A bolus of 0.1 mmol/kg of MR contrast material (gadoteridol) was injected intravenously 30 s after beginning image acquisition at a rate of 9 ml/s using a power injector. Time/signal-intensity curves to reflect the onset, slope, and relative signal intensity (rSI) of contrast enhancement in the tumor region were generated. Median follow-up was 8 months (range 3-18 months). RESULTS: Tumors with a higher tissue perfusion (rSI > or = 2.8) in the pretherapy and early therapy (20-22 Gy) studies had a lower incidence of local recurrence than those with a rSI of < 2.8, but this was not statistically significant (13% vs. 67%; p = 0.05). An increase in tumor perfusion early during therapy (20-22 Gy), particularly to an rSI of > or = 2.8, was the strongest predictor of local recurrence (0% vs. 78%; p = 0.002). However, pelvic examination during early therapy (20-22 Gy) commonly showed no appreciable tumor regression. The slope of the time/signal-intensity curve obtained before and during radiation therapy also correlated with local recurrence. Follow-up perfusion studies did not provide information to predict recurrence. CONCLUSION: These preliminary results suggest that two simple MR perfusion studies before and early in therapy can offer important information on treatment outcome within the first 2 weeks of radiation therapy before response is evident by clinical examination. High tumor perfusion before therapy and increasing or persistent high perfusion early during the course of therapy appear to be favorable signs. High perfusion suggests a high blood and oxygen supply to the tumor. The increase in tumor perfusion seen in some patients early during radiation therapy suggests improved oxygenation of previously hypoxic cells following early cell kill. Radiation therapy is more effective in eradicating these tumors, resulting in improved local control. Our technique may be helpful in identifying early-while more aggressive therapy can still be implemented-those patients who respond poorly to conventional radiation therapy.