A GPU based high-resolution multilevel biomechanical head and neck model for validating deformable image registration.

PURPOSE: Validating the usage of deformable image registration (dir) for daily patient positioning is critical for adaptive radiotherapy (RT) applications pertaining to head and neck (HN) radiotherapy. The authors present a methodology for generating biomechanically realistic ground-truth data for validating dir algorithms for HN anatomy by (a) developing a high-resolution deformable biomechanical HN model from a planning CT, (b) simulating deformations for a range of interfraction posture changes and physiological regression, and (c) generating subsequent CT images representing the deformed anatomy. METHODS: The biomechanical model was developed using HN kVCT datasets and the corresponding structure contours. The voxels inside a given 3D contour boundary were clustered using a graphics processing unit (GPU) based algorithm that accounted for inconsistencies and gaps in the boundary to form a volumetric structure. While the bony anatomy was modeled as rigid body, the muscle and soft tissue structures were modeled as mass-spring-damper models with elastic material properties that corresponded to the underlying contoured anatomies. Within a given muscle structure, the voxels were classified using a uniform grid and a normalized mass was assigned to each voxel based on its Hounsfield number. The soft tissue deformation for a given skeletal actuation was performed using an implicit Euler integration with each iteration split into two substeps: one for the muscle structures and the other for the remaining soft tissues. Posture changes were simulated by articulating the skeletal structure and enabling the soft structures to deform accordingly. Physiological changes representing tumor regression were simulated by reducing the target volume and enabling the surrounding soft structures to deform accordingly. Finally, the authors also discuss a new approach to generate kVCT images representing the deformed anatomy that accounts for gaps and antialiasing artifacts that may be caused by the biomechanical deformation process. Accuracy and stability of the model response were validated using ground-truth simulations representing soft tissue behavior under local and global deformations. Numerical accuracy of the HN deformations was analyzed by applying nonrigid skeletal transformations acquired from interfraction kVCT images to the model's skeletal structures and comparing the subsequent soft tissue deformations of the model with the clinical anatomy. RESULTS: The GPU based framework enabled the model deformation to be performed at 60 frames/s, facilitating simulations of posture changes and physiological regressions at interactive speeds. The soft tissue response was accurate with a R(2) value of >0.98 when compared to ground-truth global and local force deformation analysis. The deformation of the HN anatomy by the model agreed with the clinically observed deformations with an average correlation coefficient of 0.956. For a clinically relevant range of posture and physiological changes, the model deformations stabilized with an uncertainty of less than 0.01 mm. CONCLUSIONS: Documenting dose delivery for HN radiotherapy is essential accounting for posture and physiological changes. The biomechanical model discussed in this paper was able to deform in real-time, allowing interactive simulations and visualization of such changes. The model would allow patient specific validations of the dir method and has the potential to be a significant aid in adaptive radiotherapy techniques.

SU-E-J-201: What is the Importance of Dose Recalculation for Adaptive Radiotherapy Dose Assessment?

PURPOSE: To quantify the effect of using the planned dose distributions in lieu of performing dose recalculations on daily in-room images for adaptive radiotherapy (ART) dose assessment of head and neck cancer patients. METHODS: 16 patients with cancers of the head and neck were treated using the TomoTherapy Hi-Art II (Accuray Inc., Sunnyvale, CA). Images of all patients were acquired prior to each treatment using the megavoltage CT (MVCT) capability of the TomoTherapy unit. Overall, images from 528 fractions were evaluated. For every image set, the delivered dose was estimated by both recalculating the dose distribution using the acquired MVCT and also by simply overlaying the planned distribution on the new images. ART dose assessment was performed using deformable image registration (DIR) to deform contours from the treatment plan to the images acquired during each fraction and to accumulate the estimated dose delivered during each fraction back to the reference treatment plan. The same DIR maps were applied to both dose estimation methods. Dosimetric endpoints were then compared between the DVHs computed using the recalculated or planned dose distributions. RESULTS: The mean PTV D95% and D05% endpoints were 0.6±0.5% and 1.4±0.8% lower using the planned dose distributions compared to the recalculated distributions, respectively, across all patients. The mean parotid D50% was 2.4±1.5% greater using the planned distributions compared to the recalculated distributions. The parotid D50% from the planned distributions was also highly correlated with the parotid D50% from the recalculated distributions for each patient (mean r2=0.97±0.09). CONCLUSIONS: For this treatment modality and site, dosimetric differences observed between overlaying the planned dose distributions and recalculating distributions on daily images were typically well within ±5%. This indicates that the dose distribution itself is robust against anatomic variations. This study was funded, in part, by a grant from Accuray Inc.

A comparison of newborn stylized and tomographic models for dose assessment in paediatric radiology.

Establishment of organ doses from diagnostic and interventional examinations is a key component to quantifying the radiation risks from medical exposures and for formulating corresponding dose-reduction strategies. Radiation transport models of human anatomy provide a convenient method for simulating radiological examinations. At present, two classes of models exist: stylized mathematical models and tomographic voxel models. In the present study, organ dose comparisons are made for projection radiographs of both a stylized and a tomographic model of the newborn patient. Sixteen separate radiographs were simulated for each model at x-ray technique factors typical of newborn examinations: chest, abdomen, thorax and head views in the AP, PA, left LAT and right LAT projection orientation. For AP and PA radiographs of the torso (chest, abdomen and thorax views), the effective dose assessed for the tomographic model exceeds that for the stylized model with per cent differences ranging from 19% (AP abdominal view) to 43% AP chest view. In contrast, the effective dose for the stylized model exceeds that for the tomographic model for all eight lateral views including those of the head, with per cent differences ranging from 9% (LLAT chest view) to 51% (RLAT thorax view). While organ positioning differences do exist between the models, a major factor contributing to differences in effective dose is the models' exterior trunk shape. In the tomographic model, a more elliptical shape is seen thus providing for less tissue shielding for internal organs in the AP and PA directions, with corresponding increased tissue shielding in the lateral directions. This observation is opposite of that seen in comparisons of stylized and tomographic models of the adult.

Use of serotonergic drugs for treating depression in older patients.

The selective serotonin reuptake inhibitors (SSRIs) offer a relatively new alternative to traditional tricyclic antidepressants (TCAs) in the treatment of depression in older adults. The two drug classes are equally effective, but SSRIs tend to cause fewer sedating, anticholinergic, or hypotensive effects and are unlikely to affect cardiac conduction. SSRIs also have a wider therapeutic window and are safer in cases of overdose. Potential side effects include GI distress, worsening of headaches, insomnia, and sexual dysfunction. Drawbacks of using SSRIs are their potential for drug interactions and relatively high cost.

Reduplication after right middle cerebral artery infarction.

Reduplication and misidentification syndromes are similar and peculiar phenomena of disorientation and beliefs with delusional qualities. They are more frequent among neurologic and psychiatric patients than previously thought. Organic factors play a definitive role in their occurrence. A case is presented which exemplifies reduplication of place and person, following a right hemisphere focal lesion. Current theories are briefly reviewed and possible roles of nortriptyline therapy and psychological factors are discussed in the pathogenesis of reduplicative phenomena in this patient.

Memory and frontal lobe dysfunction in schizophrenia and schizoaffective disorder.

Verbal memory and performance on a number of tests known to be sensitive to lesions that disrupt frontal lobe functioning were studied in patients with schizophrenia or schizoaffective illness. Both patient groups were severely and equally impaired on verbal and design fluency and on the Wisconsin Card Sorting Test, measures that are sensitive to dysfunction of frontal-striatal circuitry. Both patient groups exhibited impaired recall but nearly normal recognition memory, a pattern that is typically observed in frontal and subcortical diseases. Accelerated forgetting was evident on delayed recall tests; the magnitude of this impairment was greater for schizophrenic than for schizoaffective patients. These results suggest that frontal and/or subcortical dysfunction is common to schizophrenia and schizoaffective disorder. A subgroup including the majority of schizophrenic patients, however, exhibit a mild amnesia-like disorder which may result from pathological changes in the structure and function of the temporal lobes or the medial diencephalon.

Personality characteristics of men who physically abuse women.

OBJECTIVE: Studies have suggested that personality disorders may be common among men who habitually commit domestic violence. The study reported here attempted to characterize personality traits and psychological and cognitive characteristics of men who batter women in order to distinguish them from nonbattering men. METHODS: A group of 21 batterers were compared with a group of nonbatterers using the Minnesota Multiphasic Personality Inventory and its personality disorder scales (MMPIPDS) and the Hostility and Direction of Hostility Questionnaire. Comparability of the two groups was assessed on several demographic variables and on scores on the Revised Michigan Alcoholism Screening Test, three cognitive measures, and three measures of affective disturbance. RESULTS: Batterers scored higher on only the borderline and antisocial MMPIPDS and on the acting-out hostility and self-criticism scales of the hostility questionnaire. Problem-solving skills for both of the groups were considerably poorer than published norms. No significant differences were found between the groups in age, race, education, socioeconomic status, alcohol abuse, performance on cognitive measures, depression scale scores, or overall scores on the MMPI. As children, batterers were more likely to have experienced physical or emotional abuse. CONCLUSIONS: Men who commit domestic violence may be found among a larger pool of men with poor problem-solving skills, but in addition they appear to have borderline-antisocial personality traits, certain types of hostility, and histories of abuse as children that may predispose them to become violent with their female companions.

Performance of children with ADHD on tests sensitive to frontal lobe dysfunction.

The performances of 20 children with attention deficit hyperactivity disorder (ADHD) were compared with those of 20 matched normal controls on a battery of neuropsychological tests. The ADHD children exhibited impaired function in reading comprehension, verbal learning and memory, and on the Information, Arithmetic, Digit Span, Block Design, and Coding subtests of the Wechsler Intelligence Scale for Children-Revised, but they performed nearly normally on measures of verbal and design fluency and on the Wisconsin Card Sorting Test. The hypothesis that disturbances in frontal lobe function related to impulse control may be responsible for the cognitive impairments observed in ADHD was not supported. Inability to control and direct attention appears to be more central to the pathophysiology of this disorder.

A pilot controlled study of the use of imipramine to reduce myotonia.

It has been hypothesized that myotonic dystrophy is caused by a generalized disorder of membrane aminergic and petidergic receptors. A single uncontrolled study has suggested that the affective symptomatology and muscular disability of this disorder might be improved by tricyclic antidepressant treatment. In the present study, 12 adult patients with myotonic dystrophy (age range 18-55 yr) were treated with imipramine and placebo in a double-blind crossover paradigm. Both grip and percussion myotonia were significantly improved by imipramine treatment independent of change in depressive symptomatology. Serum drug levels revealed nonlinear elimination kinetics for imipramine in this patient population.

Cognitive disturbances in Parkinson's disease.

To test the hypothesis that the cognitive impairments that accompany Parkinson's disease (PD) arise from frontal lobe dysfunction, patients with idiopathic PD and controls were tested on a neuropsychological battery that included measures of anterograde memory, visuospatial perception, and naming, as well as several tests that are known to be sensitive to lesions of the frontal lobes. PD patients of normal mental status as measured by the Mini-Mental State Examination performed normally on the naming, line orientation, and verbal recognition memory tests but exhibited deficits on verbal recall. On tests of frontal lobe function, these patients showed mild deficits on a category fluency task and on the Wisconsin Card Sorting Test. However, their errors on the latter were not typical of patients with frontal lesions, and they performed normally on a letter fluency task and exhibited normal release from proactive interference. Patients of lower than normal mental status performed poorly on nearly all of the cognitive tasks including confrontational naming, line orientation, and recognition memory, suggesting that their cerebral dysfunction extended beyond subcortical-frontal circuits. The present study supports the usefulness of the Mini-Mental State Examination for cognitive screening of PD patients, but does not support the hypothesis that the cognitive impairments in PD arise principally from disruption of frontal lobe functioning.

The electroencephalographic pattern during electroconvulsive therapy: V. Observations on the origins of phase III delta energy and the mechanism of action of ECT.

The generation of the spike-wave activity of Phase III of ECT seizures is attributed to the recurrence of synchronized, prolonged periods of intense inhibitory current flow (hyperpolarization), and associated rebound spike bursts, produced by the inhibitory circuit relationships and intrinsic electrophysiological properties of thalamic neurons. An anatomical and neurophysiological model of the development of generalized, synchronous 3-Hz spike-wave seizure activity is proposed which outlines the origin, maintenance, slowing, and termination of this fundamental seizure rhythm. Phase III inhibitory current flow (delta energy) and/or spike bursts may bring about therapeutic benefit by initiating a chain of agonist-independent and agonist-dependent events which results in long-term augmentation of serotonergic and noradrenergic neurotransmission and diminution of cholinergic neurotransmission in the forebrain. A specific anatomical and functional model of the mechanism of action of ECT is proposed, in which: (1) adrenergic and cholinergic pathways in the forebrain are assumed to be massively stimulated during ECT seizures, whereas serotonergic pathways are assumed to be inhibited during these seizures; (2) the beneficial effects of ECT are considered to be more dependent upon ECT-induced changes in 5-HT neurotransmission than upon alteration of noradrenergic function; (3) these beneficial effects involve up-regulation of 5-HT2 and down-regulation of M1- and M2-muscarinic receptor densities by both agonist-independent and agonist-dependent mechanisms, coupled with functional augmentation of noradrenergic neurotransmission; and (4) these effects may be brought about by Phase III inhibitory current flow- and/or spike burst-induced alteration of the function of second-messenger generator systems.

Transketolase abnormality in cultured fibroblasts from familial chronic alcoholic men and their male offspring.

We have investigated a thiamine-dependent enzyme, transketolase, in cultured fibroblasts from 41 human subjects, including patients with alcoholism-associated Wernicke-Korsakoff syndrome (n = 3), familial chronic alcoholic males (n = 7), their sons (n = 7), nonalcoholic men (n = 7), their male offspring (n = 7), and three generations of an Amish family (n = 10) without any history of alcoholism. This study was undertaken to delineate whether transketolase abnormality (i.e., high Michaelis Menton constant (Km) for thiamine pyrophosphate), previously reported in patients with Wernicke-Korsakoff syndrome is prevalent among familial chronic alcoholic men and their sons without prior history of alcohol abuse but who are at high risk for alcoholism. Our data suggest that an inborn error (i.e., high Km of transketolase for thiamine pyrophosphate) predisposing to thiamine deficiency diseases similar to those reported in Wernicke-Korsakoff syndrome may occur in the general population. However, for some as yet unexplained reason(s) this variant seems to occur more frequently among familial chronic alcoholic men and their male offspring without any history of alcoholism. The inheritance pattern of this enzyme variant as revealed from an Amish pedigree study may be autosomal recessive as previously suggested.

Transketolase abnormality in tolazamide-induced Wernicke's encephalopathy.

We studied a thiamine-dependent enzyme, transketolase, from fibroblasts of a diabetic patient who developed Wernicke's encephalopathy when treated with tolazamide, in order to delineate if this patient also had transketolase abnormality [high Km for thiamine pyrophosphate (TPP)], as previously reported in postalcoholic Wernicke-Korsakoff syndrome. In addition to this patient, we also studied this enzyme from three diabetic kindreds without any history of Wernicke's encephalopathy and from four normal controls. We found that the above-mentioned patient and one of the diabetic kindreds with no history of Wernicke's encephalopathy had abnormal transketolase as determined by its Km for TPP. These data suggest a similarity between postalcoholic Wernicke-Korsakoff syndrome and the patient with tolazamide-induced Wernicke's encephalopathy from the standpoint of transketolase abnormality.

Adrenal steroid responses to continuous intravenous adrenocorticotropin infusion compared to bolus injection in normal volunteers.

We compared the adrenal steroid responses after synthetic ACTH-(1-24) (Cosyntropin) administration given by either continuous iv infusion or bolus injection in 11 normal women and 6 normal men. Each subject received 250 micrograms Cosyntropin as a bolus iv injection on 1 occasion and as a continuous 2-h iv infusion on another occasion, in random order. There was a 1-week interval between the studies. We measured the plasma levels of cortisol, 11-deoxycortisol, 17-hydroxyprogesterone, progesterone, pregnenolone, 17-hydroxypregnenolone, dehydroepiandrosterone, dehydroepiandrosterone sulfate, delta 5-androstenediol, androstenedione, and testosterone by RIA 15 and 0 min before and 30, 45, 60, and 120 min after administering ACTH. The steroid concentrations and their increments, ratios, or areas above baseline did not differ significantly between the bolus injection and the continuous infusion. Thus, at the dose of 250 micrograms, a bolus ACTH injection stimulates adrenal steroid secretion as effectively as a 2-h continuous ACTH infusion.

The electroencephalographic pattern during electroconvulsive therapy. IV. Spectral energy distributions with methohexital, innovar and ketamine anesthesias.

During Phase III of nondominant unilateral ECT seizures, total energy, total peak energy, total delta energy, and 1/2-power duration of total delta energy are all less (shorter) in the unstimulated, dominant hemisphere than they are in the stimulated hemisphere. Interhemispheric differences in total energy are greatest in the lateral frontotemporal cortex, where they average 40 percent with both methohexital and ketamine anesthesias in F8 greater than F7 and T4 greater than T3. This circumstance probably explains the characteristic memory sparing associated with nondominant unilateral ECT. The magnitudes of total and peak energies in each frequency band decrease in the order: delta greater than theta greater than alpha greater than beta. Delta energy constitutes approximately three-fourths of the unilateral ECT seizure's total energy, and Phase III delta energy may be the therapeutically effective agent in this treatment. Seizures induced during ketamine anesthesia are associated with a higher percentage of delta energy, with higher magnitudes of total energy and of total and peak delta energy, and with longer 1/2-power durations of delta energy. Nondominant unilateral ECT with ketamine anesthesia offers promise as the treatment of choice for patients resistant to ECT administered with methohexital anesthesia.

The electroencephalographic pattern during electroconvulsive therapy. III. Analysis of frontotemporal and nasopharyngeal spectral energy.

This study analyzes the frontotemporal and nasopharyngeal spectral energy of an ECT-induced seizure, in order to investigate the origin of the final Phase III activity, which contains most of the seizure's energy. Data supports these findings: energy in the delta frequency band is responsible for the generation, propagation, and maintenance of Phase III of the ECT-induced seizure; the synchronous "delta-firing" depolarizations of Phase III are recurrently initiated by an ECT-induced "generator" process; higher magnitudes of energy are generated centrally than are generated laterally during Phase III; and the lessened memory impairment associated with nondominant unilateral ECT is attributable to the markedly lower peak and total energies observed in the unstimulated temporal lobe.

Antidepressant treatment of children: clinical relapse is unrelated to tricyclic plasma concentrations.

Plasma concentrations of imipramine and amitriptyline and their desmethylated metabolites were measured in 20 children being treated for major depressive illness 2 wk. and 5 to 10 wk. after achieving drug dosages of 2.25 mg/kg body weight. At 2 wk. all children had exhibited clinical improvement, but by 10 wk. 4 of the 10 children treated with imipramine and 5 of the 10 children treated with amitriptyline had experienced clinical relapse of depressive symptoms. Tricyclic antidepressant plasma concentrations and ratios were comparable in the subgroups of children who maintained their clinical improvement and those who relapsed. There was no evidence of a systematic decline in plasma tricyclic antidepressant concentrations in those children who relapsed.