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Biomedical subjects

Michael L J Apuzzo

Publications and source records attributed to Michael L J Apuzzo.

At least 19 recordsLinked to original sources

Stereotactic radiosurgery: adjacent tissue injury and response after high-dose single fraction radiation: Part I--Histology, imaging, and molecular events.

Radiosurgery is now the preferred treatment modality for many intracranial disease processes. Although almost 50 years have passed since it was introduced as a tool to treat neurological disease, investigations into its effects on normal tissues of the central nervous system are still ongoing. The need for these continuing studies must be underscored. A fundamental understanding of the brain parenchymal response to radiosurgery would permit development of strategies that would enhance and potentiate the radiosurgical treatment effects on diseased tissue while mitigating injury to normal structures. To date, most studies on the response of the central nervous system to radiosurgery have been performed on brain tissue in the absence of pathological lesions, such as benign tumors or metastases. Although instructive, these investigations fail to emulate the majority of clinical scenarios that involve radiosurgical treatment of specific lesions surrounded by normal brain parenchyma. This article is the first in a two-part series that addresses the brain parenchyma's response to radiosurgery. This first article analyzes the histological, radiographic, and molecular data gathered regarding the brain parenchymal response to radiosurgery and aims to suggest future studies that could enhance our understanding of the topic. The second article in the series begins by discussing strategies for radiosurgical therapeutic enhancement. It concludes by focusing on strategies for mitigation and repair of radiation-induced brain injury.

Animals↗

Toward the emergence of nanoneurosurgery: part II--nanomedicine: diagnostics and imaging at the nanoscale level.

THE NOTION OF nanotechnology has evolved since its inception as a fantastic conceptual idea to its current position as a mainstream research initiative with broad applications among all divisions of science. In the first part of this series, we reviewed the structures and principles that comprise the main body of knowledge of nanoscience and nanotechnology (58). This article reviews and discusses the applications of nanotechnology to biological systems that will undoubtedly transform the foundations of disease diagnosis, treatment, and prevention in the future. Specific attention is given to developments in diagnostics and imaging at the nanoscale level. The use of nanoparticles and nanomaterials as biodetection agents for deoxyribonucleic acid and proteins is presented. In addition, nanodevices, such as nanowires, nanotubes, and nanocantilevers, can be combined with nanoarrays and nanofluidics to create integrated and automated nanodetection platforms. Molecular imaging modalities based on quantum dots and magnetic nanoparticles are also discussed. This technology has been extended to the imaging of intracranial neoplasms. Further innovation within these disciplines will form the basis for the development of mature nanomedicine. The final article of the series will focus on additional advancements in nanomedicine, namely nanotherapy and nanosurgery, and will cover the innovations that will lead to the eventual realization of nanoneurosurgery.

Animals↗

Toward the emergence of nanoneurosurgery: part III--nanomedicine: targeted nanotherapy, nanosurgery, and progress toward the realization of nanoneurosurgery.

The notion of nanotechnology has evolved since its inception as a fantastic conceptual idea to its current position as a mainstream research initiative with broad applications among all divisions of science. In the first part of this series, we reviewed the structures and principles that comprise the main body of knowledge of nanoscience and nanotechnology. In the second part, we discussed applications of nanotechnology to the emerging field of nanomedicine, with specific attention on medical diagnostics and imaging. This article further explores the applications of nanotechnology to nanomedicine. Specific attention is given to developments in therapeutic modalities, including advanced drug delivery systems and targeted nanotherapy, which will form the basis for the treatment arm of mature nanomedicine. A variety of modalities are discussed, including polymeric nanoparticles, micelles, liposomes, dendrimers, fullerenes, hydrogels, nanoshells, and smart surfaces. Applications of nanotechnology to nanosurgery and nanoneurosurgery are presented. Femtosecond laser systems, nanoneedles, and nanotweezers are presented as technologies that are operational at the nanoscale level and have the potential to revolutionize the practice of neurosurgery in a profound and momentous way.

Genetic Therapy↗

Robotic virtual endoscopy: development of a multidirectional rigid endoscope.

INTRODUCTION: The use of neuroendoscopy has increased in the past 20 years. Despite an increase in the number of indications for use, novel adjuncts and modifications to existing endoscopes remain all but nonexistent. We introduce a robotic virtual endoscope with applications for neurosurgery that could serve as a novel step in the evolution of future endoscopic technologies. METHODS: Over the past 8 years, we have worked on the construction of a prototype endoscope with three degrees of freedom that was designed to allow for enhanced safety while maximizing the benefits of virtual field rendition and robotic control. We have developed a prototype to examine a cerebral ventricular model in vitro that functions via either a direct video- or computer-based interface. RESULTS: Assessment of viewing angulation with robotic feedback has verified the accuracy of the prototype. Models support the ability of the endoscope to localize regions identified via a software interface. CONCLUSION: The endoscope is a rigid virtual robotic endoscope that provides complete visual coverage of a three-dimensional space by controlling an adjustable viewing direction with three degrees of freedom.

Endoscopes↗

Surgery of the mind and mood: a mosaic of issues in time and evolution.

The prevalence and economic burden of neuropsychiatric disease are enormous. The surgical treatment of these psychiatric disorders, although potentially valuable, remains one of the most controversial subjects in medicine, as its concept and potential reality raises thorny issues of moral, ethical, and socioeconomic consequence. This article traces the roots of concept and surgical efforts in this turbulent area from prehistory to the 21st century. The details of the late 19th and 20th century evolution of approaches to the problem of intractable psychiatric diseases with scrutiny of the persona and contributions of the key individuals Gottlieb Burckhardt, John Fulton, Egas Moniz, Walter Freeman, James Watts, and William Scoville are presented as a foundation for the later, more logically refined approaches of Lars Leksell, Peter Lindstrom, Geoffrey Knight, Jean Talaraich, and Desmond Kelly. These refinements, characterized by progressive minimalism and founded on a better comprehension of underlying pathways of normal function and disease states, have been further explored with recent advances in imaging, which have allowed the emergence of less invasive and technology driven non-ablative surgical directives toward these problematical disorders of mind and mood. The application of therapies based on imaging comprehension of pathway and relay abnormalities, along with explorations of the notion of surgical minimalism, promise to serve as an impetus for revival of an active surgical effort in this key global health and socioeconomic problem. Eventual coupling of cellular and molecular biology and nanotechnology with surgical enterprise is on the horizon.

Europe↗

Gamma knife radiosurgery for trigeminal neuralgia.

OBJECTIVE: The purpose of this study was to assess outcomes in patients treated with gamma knife radiosurgery for trigeminal neuralgia. METHODS: From 1997 to 2003, a total of 49 patients with trigeminal neuralgia underwent gamma knife radiosurgery. The trigeminal root entry zone immediately adjacent to the pons was targeted by use of a 4-mm collimator to deliver 40 Gy to the 50% isodose line (maximum dose, 80 Gy). Special care was taken to limit radiation dose to the adjacent pons to 12 Gy. Of the 49 study patients, all had undergone previous medical therapy, 8 (16%) had undergone microvascular decompression, 8 (16%) had undergone percutaneous rhizotomy, 2 (4%) had undergone linear accelerator-based radiosurgery, and 5 (10%) presented with multiple sclerosis. The median duration of symptoms was 6 years. There were 29 female patients (59%) and 20 male patients (41%). Facial pain outcomes were assessed by use of the Barrow Neurological Institute pain score. Other outcomes assessed included recurrence of symptoms and treatment toxicity. The median follow-up period was 49 months. RESULTS: At last evaluation, a total of 27 patients (61%) with idiopathic trigeminal neuralgia reported pain relief (scores of IIIb or less). This included 14 patients (32%) who reported complete pain relief when not receiving medications. Significant recurrence of pain after an initial interval of relief was reported by 10 patients (23%). Mean time to pain recurrence was 9.6 months (range, 2-36 mo). Mild to moderate facial numbness was experienced by 13 patients (29%), whereas 8 (18%) reported mild dysesthesias. CONCLUSION: Gamma knife radiosurgery established durable pain relief in 61% of patients with medically refractory idiopathic trigeminal neuralgia. A longer follow-up period is necessary to fully assess the incidence of late complications and recurrences.

Adult↗

A fantastic voyage: a personal perspective on involvement in the development of modern stereotactic and functional neurosurgery (1974-2004).

Stressing environments, individuals, ideas, and global events, this historical stereotactic and functional neurosurgical vignette initially presents a review of factors in the genesis of personal interest and the foundations of involvement in the discipline of neurological surgery. The vignette then traces the development of concepts and instrumentation and their ultimate practical utilization in patient care on the neurosurgical services at the Keck School of Medicine at the University of Southern California over the course of a 3-decade period (1974-2004). The article summarizes and elaborates details of contributions to the literature and complex involvement on the national and international levels as the refinements and capabilities of stereotactic and functional neurosurgery have been reinvented over a generation through the emergence of new technology, ideas, individual ingenuity, and active collegial exchange.

Europe↗

Toward the emergence of nanoneurosurgery: part I--progress in nanoscience, nanotechnology, and the comprehension of events in the mesoscale realm.

Since its original conception in 1959, the notion of nanotechnology and its potential ramifications have not only created fascination, but also intense scientific effort and scrutiny. Currently, research activities are being principally conducted in mesoscale, the realm between nanoscale and macroscale, with the rudiments of nanoscience being defined in realities and principles that will determine activities and discoveries in the future. This paper reviews and discusses the evolution of nanoscience, its contemporary status, and the discoveries that currently constitute the main components of the body of knowledge from a neurosurgical perspective. Specific attention is given to the developments in imaging, fabrication, nanostructures, nanoelectromechanical systems, molecular manufacturing, nanocomputation, and emerging physical and chemical concepts in mesoscale, as they will establish foundations for the realization of nanomedicine and nanoneurosurgery.

Humans↗

Vector analysis correlating bullet trajectory to outcome after civilian through-and-through gunshot wound to the head: using imaging cues to predict fatal outcome.

OBJECTIVE: We identify radiographic imaging similarities found on head computed tomographic (CT) scans of patients with through-and-through gunshot wounds to the head with fatal outcomes. METHODS: A retrospective analysis was conducted over an 18-month period from June 2001 through December 2002. Two hundred seventeen gunshot wound patients were evaluated. Exclusion criteria included any patient with cardiopulmonary injury and instability, airway compromise, or extracranial injuries affecting prognosis. Thirty-seven patients with isolated gunshot wounds to the head were included, 10 of which were fatal. Vital signs, examination results, Glasgow coma scale (GCS) score, intracranial pressure monitoring, surgical data, days in the intensive care unit, and CT scan appearance were collected. A Cartesian xyz coordinate system was created centered on the dorsum sella. Bullet pathways on CT scans were plotted and graphed onto a standardized magnetic resonance imaging scan. RESULTS: Ten patients progressed to brain death. GCS score and pupil irregularity were associated with fatal outcome (P < 0.0001). CT scans showed that brain shift was more common in survivors. Seventy percent of nonsurvivors had minimal brain shift. A tram-track sign on CT scans correlated with fatal outcome (P = 0.005). Vector analysis of nonsurvivors showed an area of the brain approximately 4 cm above the dorsum sella that, when penetrated through the midline, led to brain death (P = 0.0006). This zone was coined the zona fatalis. CONCLUSION: We confirm that GCS score and diabetes insipidus correlated with fatal outcome. In the setting of low-velocity gunshot wounds, fatal outcome and low GCS score were associated with a tram-track sign on CT scans. Bullet passage through a particular supra-dorsum sellar transventricular zone was associated with fatal outcome.

Adolescent↗

The physics of image formation in the neuroendoscope.

INTRODUCTION: The development of the neuroendoscope has allowed neurosurgeons to visualize anatomic structures deep within the nervous system with minimal disruption of the critical overlying structures. This has enabled the development of an entire system of tools and techniques for maximum effective action at the target point through minimal corridors for the treatment of an entire spectrum of pathologies. DISCUSSION: The design of an optical instrument with the ability to illuminate deep, hidden anatomic structures and transmit those images accurately and brightly to the eye of the neurosurgeon poses several challenges. These challenges have been met by advances in lens design and optical systems engineering over a period of several decades leading up to emergence of the modern neuroendoscope. In this paper, the basic concepts of the physics of image formation in optical systems are reviewed with emphasis on those elements critical to the endoscope. CONCLUSION: A consideration of these basic concepts is critical to the understanding of the limitations and capabilities of the key instrument for neuroendoscopy.

Humans↗

The evolution and future of minimalism in neurological surgery.

INTRODUCTION: The evolution of the field of neurological surgery has been marked by a progressive minimalism. This has been evident in the development of an entire arsenal of modern neurosurgical enterprises, including microneurosurgery, neuroendoscopy, stereotactic neurosurgery, endovascular techniques, radiosurgical systems, intraoperative and navigational devices, and in the last decade, cellular and molecular adjuvants. AIMS: In addition to reviewing the major developments and paradigm shifts in the cyclic reinvention of the field as it currently stands, this paper attempts to identify forces and developments that are likely to fuel the irresistible escalation of minimalism into the future. These forces include discoveries in computational science, imaging, molecular science, biomedical engineering, and information processing as they relate to the theme of minimalism. DISCUSSION: These areas are explained in the light of future possibilities offered by the emerging field of nanotechnology with molecular engineering.

Biomedical Engineering↗

Measurements of the relative output factors for CyberKnife collimators.

OBJECTIVE: To determine accurately the relative output factors, defined as the ratio of the nominal dose rate for a given collimator to that of the 60-mm collimator. This is particularly important for radiosurgical treatment of functional disorders, such as trigeminal neuralgia, in which a single large radiation dose is delivered to the target with a small collimator, such as the 5-mm collimator for CyberKnife radiosurgery. Numerous studies on the output factors have been reported for the Leksell gamma knife unit but none for the CyberKnife system. METHODS: Measurements of the relative output factors for all 12 collimators were performed by three different methods: silicon diode, radiographic film, and thermoluminescent dosimetry microcubes. The silicon diode is designed for measurements in small (1-50 MV) photon beams performed in water or air. Film and thermoluminescent dosimetry measurements were performed in a plastic phantom. RESULTS: The measured relative output factors for the three methods were very similar except for the three smallest collimators (5, 7.5, and 10 mm). The measured difference between the above methods was approximately 2%. The mean value of the output factor for the 5-mm collimator was 0.686 +/- 0.024. The uncertainties of the output factors are expected to increase with the decrease of collimator diameter. They range from approximately 1 to 4% of the relative output factor. CONCLUSION: The relative output factor can be measured with an acceptable accuracy even for the smallest (5-mm) CyberKnife collimators. This requires the selection of appropriate dosimetric detectors and measuring procedures. The results obtained with the diode are considered more accurate than with the other two methods.

Film Dosimetry↗

Virtual reality neurosurgery: a simulator blueprint.

OBJECTIVE: This article details preliminary studies undertaken to integrate the most relevant advancements across multiple disciplines in an effort to construct a highly realistic neurosurgical simulator based on a distributed computer architecture. Techniques based on modified computational modeling paradigms incorporating finite element analysis are presented, as are current and projected efforts directed toward the implementation of a novel bidirectional haptic device. METHODS: Patient-specific data derived from noninvasive magnetic resonance imaging sequences are used to construct a computational model of the surgical region of interest. Magnetic resonance images of the brain may be coregistered with those obtained from magnetic resonance angiography, magnetic resonance venography, and diffusion tensor imaging to formulate models of varying anatomic complexity. RESULTS: The majority of the computational burden is encountered in the presimulation reduction of the computational model and allows realization of the required threshold rates for the accurate and realistic representation of real-time visual animations. CONCLUSION: Intracranial neurosurgical procedures offer an ideal testing site for the development of a totally immersive virtual reality surgical simulator when compared with the simulations required in other surgical subspecialties. The material properties of the brain as well as the typically small volumes of tissue exposed in the surgical field, coupled with techniques and strategies to minimize computational demands, provide unique opportunities for the development of such a simulator. Incorporation of real-time haptic and visual feedback is approached here and likely will be accomplished soon.

Computer Simulation↗

Study of magnetic resonance imaging-based arteriovenous malformation delineation without conventional angiography.

OBJECTIVE: In this study, we aimed to assess the feasibility of arteriovenous malformation (AVM) delineation for gamma knife radiosurgery without conventional angiography and to correlate factors that may affect AVM delineation. METHODS: A series of 57 consecutive patients with AVMs treated with gamma knife radiosurgery from August 1994 to December 2000 were reviewed. All patients in the study had undergone pretreatment angiography. The mean AVM volume was 2.8 cm(3), with a median of 2.0 cm(3) (range, 0.04-22 cm(3)). All AVMs were delineated on the original frame-based magnetic resonance imaging (MRI) scans by a vascular neurosurgeon without the assistance of angiography and then compared with the actual AVM delineation on the basis of previously performed angiography and MRI. Univariate correlation analysis was used to determine the relationship of AVM coverage, size, diffuseness, previous embolization, and hemorrhage parameters. RESULTS: The study volume or MRI-based volume alone coincided with the actual treatment volume by a mean of 58% for diffuse and 87% for nondiffuse AVMs (P = 0.0005). At AVM volume greater than 2 cm(3), the median percentage of coinciding volume was 63% for embolized AVMs and 82% for nonembolized AVMs (P = 0.0315). Conversely, the study volume overestimated the actual treatment volume by a mean of 57% for AVMs larger than 2 cm(3) versus 25% for AVMs smaller than 2 cm(3) (P = 0.0012). In general, the percentage of the coinciding volume was inversely related to that of the excess volume, whereas both the study volume and the coinciding volume were proportionate to AVM volume at treatment. CONCLUSION: MRI-based AVM delineation without conventional angiography may be feasible only for selected patients, such as those with nondiffuse and large nonembolized AVMs.

Adolescent↗

Reliability of three-dimensional fluoroscopy for detecting pedicle screw violations in the thoracic and lumbar spine.

OBJECTIVE: Thoracic and lumbar pedicle screws have become popular because of their biomechanical superiority over other methods of spinal fixation. However, the safety and efficacy of transpedicular screws depend on their proper placement. Recent advances in imaging have resulted in the ability to acquire three-dimensional (3-D) axial images of the spine during surgery, and this study was undertaken to assess the reliability of this technology to detect pedicle violations. METHODS: Pedicle screws were placed in six human cadaver spines from T1 to S1 using standard techniques. Intentional pedicle violations were created in 74 of 216 pedicles, and violations were graded on a four-point scale (range, 0-3). Radiographic images were then obtained using a conventional spiral computed tomographic scanner and the Siremobil Iso-C 3D (Siemens Medical Solutions, Erlangen, Germany) 3-D fluoroscopy unit. An independent neuroradiologist then graded pedicle violations as ascertained by the two imaging modalities. RESULTS: Using direct inspection of the pedicles as the "gold standard," the overall sensitivity and specificity for detecting pedicle violations were 0.716 and 0.789, respectively, with 3-D fluoroscopy. The overall sensitivity and specificity for detecting pedicle violations were 0.608 and 0.937, respectively, with conventional computed tomography. All Grade 2 pedicle violations were detected in the thoracic spine by both modalities, and all Grade 3 violations were detected by both modalities. CONCLUSION: Axial images obtained with 3-D fluoroscopy demonstrate a higher sensitivity but lower specificity than conventional computed tomographic scanning for assessing pedicle violations. By providing real-time intraoperative imaging, 3-D fluoroscopy may enhance the safety of thoracic transpedicular instrumentation.

Bone Screws↗

Gamma knife radiosurgery for benign cavernous sinus tumors: quantitative analysis of treatment outcomes.

OBJECTIVE: We review our 8-year experience with gamma knife radiosurgery (GKRS) for the treatment of patients with benign cavernous sinus tumors and present a quantitative analysis of factors relevant to treatment outcomes. METHODS: From 1994 to 2002, a total of 139 patients with benign cavernous sinus tumors were treated in 145 sessions. Their median age was 53 years, and the median follow-up was 3.5 years. The tumors included 57 meningiomas, 76 pituitary tumors (49 nonfunctional adenomas, 15 prolactinomas, 5 adrenocorticotropic hormone-secreting tumors, 6 growth hormone-secreting tumors, and 1 plurihormone-secreting tumor), 4 schwannomas, 1 hemangioma, and 1 paraganglioma. Sekhar tumor grades were as follows: I, n = 28 (20%); II, n = 42 (30%); III, n = 42 (30%); IV, n = 19 (14%); and V, n = 8 (6%). The median tumor volume was 3.4 cm(3), and the median prescribed dose was 15 Gy defined to the 50% isodose line. RESULTS: A total of 136 treated tumors (97.8%) were well controlled by GKRS, with low morbidity. For meningiomas, 29 tumors (51%) were unchanged and 26 (46%) were smaller at a median of 15.2 months. For pituitary tumors, 50 (66%) were unchanged and 25 (33%) were smaller at a median of 20.6 months. Improvement in cranial nerve (CN) function was seen in 19 (36.5%) of 52 patients with pre-GKRS deficits, and 3 patients (2.2%) developed new stable CN deficits after GKRS: 1 patient developed IVth CN palsy at 9 months, and 2 developed persistent VIth CN palsies at 43 and 45 months, respectively, that required surgical correction. Two patients developed transient VIth CN palsies at 48 months that self-resolved after another year. Endocrine function normalized for all 6 treated patients with a growth hormone-secreting tumor at a median of 18 months. One of the 5 adrenocorticotropic hormone-secreting tumors required retreatment after 17 months because of continued cortisol elevation. Thirteen (87%) of 15 prolactinoma patients had normalized prolactin levels within 2 years of the procedure; 2 patients relapsed by endocrine criteria at 18 and 22 months after GKRS. Two patients with normalized prolactin levels completed three normal pregnancies within 3 years of treatment. Six patients (4.3%) with a median tumor volume of 8 cm(3) developed radiation-induced injury at a median of 36 months after GKRS. Five of these patients also underwent external beam radiotherapy and received a median dose of 52.2 Gy in 30 fractions. Quantitative analysis revealed that the radiation dose to critical structures (optic apparatus and pons) is correlated with their distance from tumor margins. Underdosed tumor volume, tumor volume, and total treated volume are correlated with treatment outcomes. CONCLUSION: GKRS is a safe and effective treatment for selected patients with benign cavernous sinus tumors and is an important adjunct for treating postoperative tumor residual and/or recurrent tumor. Continued analysis of treated patients over an extended time is needed to evaluate long-term disease control and potential late GKRS complications.

Adolescent↗

The Leksell gamma knife Model U versus Model C: a quantitative comparison of radiosurgical treatment parameters.

OBJECTIVE: We present a quantitative comparison of radiosurgery treatments for cavernous sinus tumors using the Leksell gamma knife Model U versus the Model C with automatic positioning system (APS) (Elekta Instruments, Norcross, GA). METHODS: At our medical center from August 1994 through May 2000, the Model U was used to treat 96 patients (37 men [39%] and 59 women [61%]; median age, 54.5 yr) with benign cavernous sinus tumors: 43 meningiomas (45%), 48 pituitary tumors (50%), and 5 others (5%). From June 2000 through April 2002, the Model C with APS treated 45 patients (20 men [44%] and 25 women [56%]; median age, 51.4 yr) with 15 meningiomas (33%), 29 pituitary tumors (65%), and 1 schwannoma (2%). The two groups had similar treated tumor volumes (Model U mean, 4.3 cm(3); Model C mean, 4.2 cm(3)), equivalent tumor distances from critical structures (optic nerve, chiasm, and pons), comparable distributions in Sekhar tumor grades, and the same median prescribed dose of 15 Gy to the 50% isodose line at the tumor periphery. All planning and treatments were performed by the same radiosurgery team to minimize dosage to adjacent critical tissues and to optimize conformity index. RESULTS: Analysis of multiple treatment parameters showed that the Model C plans were superior. Model C treatments had an improved conformity index (Model U mean, 1.7; Model C mean, 1.6; P < 0.02) and a lower underdosed tumor volume (Model U mean, 0.4 cm(3); Model C mean, 0.1 cm(3); P < 0.004). The total treated volume and the excess treated volume were similar. The Model C group had a reduction in optic chiasm dose (Model C mean dose, 3.8 Gy; Model U mean dose, 5.3 Gy; P < 0.0001). The average number of isocenters was slightly higher for the Model C group (6.7 versus 6 for the Model U), but with a lower mean number of collimator sizes (1 versus 2 for the Model U). Model C plans required a mean of 93 fewer plugs per treatment, thus contributing to an estimated 67.6 minutes saved per treatment session. CONCLUSION: Comparison of radiosurgery treatments using the Leksell gamma knife Model U versus the Model C with APS was performed by quantitative analysis of treatment parameters on a cohort of benign cavernous sinus tumors. Treatment plans using the Model C resulted in better tumor coverage (improved conformity, less underdosed tumor volume) and decreased optic chiasm dose. An estimated average of 1 hour was saved per treatment when using the Model C with APS.

Adolescent↗