Feasibility of using a transmission ion chamber for QA tests of medical linear accelerators.

PURPOSE: To study the feasibility of using the Integral Quality Monitoring (IQM) system for routine quality assurance (QA) of photon beams. METHODS: The IQM system is a commercially available dose delivery verification tool, which consists of a spatially sensitive large area transmission ion chamber, mounted on the Linac collimator, and a calculation algorithm to predict the signals in response to radiation beams. By comparing the measured and predicted signals the system verifies the accuracy of beam delivery. The ion chamber unit is a battery powered system including a dual-electrometer, temperature and pressure sensors, and inclinometers. The feasibility of using the IQM system for routine QA tests was investigated by measuring constancy values of beam parameters, with specially designed tests fields, and comparing them with those determined by a conventional system. RESULTS: The sensitivity of the beam output constancy measurements by the IQM system was found to agree with those measured by a Farmer type ion chamber placed in water phantoms to within 0.1% for typical daily output variation of ± 0.5% and ± 1%. The beam symmetry was measured with a 4 cm × 4 cm aperture at multiple off-axis distances and was found to have a highly linear relationship with those measured in a water phantom scan for intentionally introduced asymmetry between -3% and +3%. The beam flatness was measured with a two-field ratio method and was found to be linearly correlated with those measured by water phantom scan. The dosimetric equivalent of a picket fence test performed by the IQM system can serve as a constancy check of the multileaf collimator (MLC) bank positioning test. CONCLUSIONS: The IQM system has been investigated for constancy measurements of various beam parameters for photon beams. The results suggest that the system can be used for most of the routine QA tests effectively and efficiently.

AAPM task group report 275.S: Survey strategy and results on plan review and chart check practices in US and Canada.

BACKGROUND: AAPM Task Group (TG) 275 was charged with developing practical, evidence-based recommendations for physics plan and chart review clinical processes for radiation therapy. As part of this charge, and to characterize practices and clinical processes, a survey of the medical physics community was developed and conducted. Detailed analyses and trends based on the survey that exceeded TG report length constraints are presented herein. AIMS: The design, development, and detailed results of the TG- 275 survey as well as statistical analysis and trends are described in detail. This is complementary material to the TG 275 report. METHODS AND MATERIALS: The survey consisted of 100 multiple-choice questions divided into four main sections: 1) Demographics, 2) Initial Plan Check, 3) On-Treatment, and 4) End-of-Treatment Chart Check. The survey was released to all AAPM members who self-reported working in the radiation oncology field, and it was kept open for 7 weeks. Results were summarized using descriptive statistics. To study practice differences, tests of association were performed using data grouped by four demographic questions: 1) Institution Type, 2) Average number of patients treated daily, 3) Radiation Oncology Electronic Medical Record, and 4) Perceived Culture of Safety. RESULTS: The survey captured 1370 non-duplicate entries from the United States and Canada. Differences across practices were grouped and presented based on Process-Based and Check-Specific questions. A risk-based summary was created to show differences amongst the four demographic questions for checks associated with the highest risk failure modes identified by TG-275. CONCLUSION: The TG-275 survey captured a baseline of practices on initial plan, on-treatment, and end-of-treatment checks across a wide variety of clinics and institutions. The results of test of association showed practice heterogeneities as a function of demographic characteristics. Survey data were successfully used to inform TG-275 recommendations.

Medical physics practice guideline 4.b: Development, implementation, use and maintenance of safety checklists.

The American Association of Physicists in Medicine (AAPM) is a nonprofit professional society whose primary purposes are to advance the science, education, and professional practice of medical physics. The AAPM has more than 8000 members and is the principal organization of medical physicists in the US. The AAPM will periodically define new practice guidelines for medical physics practice to help advance the science of medical physics and to improve the quality of service to patients throughout the US. Existing medical physics practice guidelines will be reviewed for the purpose of revision or renewal, as appropriate, on their fifth anniversary or sooner. Each medical physics practice guideline represents a policy statement by the AAPM, has undergone a thorough consensus process in which it has been subjected to extensive review, and requires the approval of the Professional Council. The medical physics practice guidelines recognize that the safe and effective use of diagnostic and therapeutic radiology requires specific training, skills, and techniques, as described in each document. Reproduction or modification of the published practice guidelines and technical standards by those entities not providing these services is not authorized. The following terms are used in the AAPM practice guidelines: Must and must not: Used to indicate that adherence to the recommendation is considered necessary to conform to this practice guideline. While must is the term to be used in the guidelines, if an entity that adopts the guideline has shall as the preferred term, the AAPM considers that must and shall have the same meaning. Should and should not: Used to indicate a prudent practice to which exceptions may occasionally be made in appropriate circumstances.

Rectal ultrasound as unique diagnostic option in obstructive colorectal metastasis from breast adenocarcinoma.

We present the case of an uncommon manifestation of metastatic breast cancer as an occlusive colorectal stenosis with submucosal location. The endoscopic rectal ultrasound allowed to confirm the diagnosis with transmural biopsies.

Cross Talk Between Brain Innate Immunity and Serotonin Signaling Underlies Depressive-Like Behavior Induced by Alzheimer's Amyloid-ß Oligomers in Mice.

Considerable clinical and epidemiological evidence links Alzheimer's disease (AD) and depression. However, the molecular mechanisms underlying this connection are largely unknown. We reported recently that soluble Aß oligomers (AßOs), toxins that accumulate in AD brains and are thought to instigate synapse damage and memory loss, induce depressive-like behavior in mice. Here, we report that the mechanism underlying this action involves AßO-induced microglial activation, aberrant TNF-α signaling, and decreased brain serotonin levels. Inactivation or ablation of microglia blocked the increase in brain TNF-α and abolished depressive-like behavior induced by AßOs. Significantly, we identified serotonin as a negative regulator of microglial activation. Finally, AßOs failed to induce depressive-like behavior in Toll-like receptor 4-deficient mice and in mice harboring a nonfunctional TLR4 variant in myeloid cells. Results establish that AßOs trigger depressive-like behavior via a double impact on brain serotonin levels and microglial activation, unveiling a cross talk between brain innate immunity and serotonergic signaling as a key player in mood alterations in AD. SIGNIFICANCE STATEMENT: Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the main cause of dementia in the world. Brain accumulation of amyloid-ß oligomers (AßOs) is a major feature in the pathogenesis of AD. Although clinical and epidemiological data suggest a strong connection between AD and depression, the underlying mechanisms linking these two disorders remain largely unknown. Here, we report that aberrant activation of the brain innate immunity and decreased serotonergic tonus in the brain are key players in AßO-induced depressive-like behavior in mice. Our findings may open up new possibilities for the development of effective therapeutics for AD and depression aimed at modulating microglial function.

Prion Protein Modulates Monoaminergic Systems and Depressive-like Behavior in Mice.

We sought to examine interactions of the prion protein (PrP(C)) with monoaminergic systems due to: the role of PrP(C) in both Prion and Alzheimer diseases, which include clinical depression among their symptoms, the implication of monoamines in depression, and the hypothesis that PrP(C) serves as a scaffold for signaling systems. To that effect we compared both behavior and monoaminergic markers in wild type (WT) and PrP(C)-null (PrP(-/-)) mice. PrP(-/-) mice performed poorly when compared with WT in forced swimming, tail suspension, and novelty suppressed feeding tests, typical of depressive-like behavior, but not in the control open field nor rotarod motor tests; cyclic AMP responses to stimulation of D1 receptors by dopamine was selectively impaired in PrP(-/-) mice, and responses to serotonin, but not to norepinephrine, also differed between genotypes. Contents of dopamine, tyrosine hydroxylase, and the 5-HT5A serotonin receptor were increased in the cerebral cortex of PrP(-/-), as compared with WT mice. Microscopic colocalization, as well as binding in overlay assays were found of PrP(C) with both the 5HT5A and D1, but not D4 receptors. The data are consistent with the scaffolding of monoaminergic signaling modules by PrP(C), and may help understand the pathogenesis of clinical depression and neurodegenerative disorders.

USP46: a new piece of the memory puzzle?

Long-term potentiation (LTP) and long-term depression (LTD) are crucial for synaptic plasticity, and are driven by AMPA receptor (AMPAR) trafficking. Recent findings indicate that the ubiquitin-proteasome system, the main protein degradation machinery of the cell, plays a significant role in memory formation by regulating the induction and maintenance of LTP. Although previously suggested as a possibility, deubiquitination of mammalian AMPARs had not been demonstrated, and the search for an enzyme that mediates the processes continued. This Editorial Highlight discusses the relevance of a study published in the current issue of Journal of Neurochemistry, in which the authors Huo and collaborators now identified ubiquitin-specific peptidase 46 (USP46) as a specific AMPAR deubiquitinase.

Medical Physics Practice Guideline 4.a: Development, implementation, use and maintenance of safety checklists.

The American Association of Physicists in Medicine (AAPM) is a nonprofit professional society whose primary purposes are to advance the science, education and professional practice of medical physics. The AAPM has more than 8,000 members and is the principal organization of medical physicists in the United States.The AAPM will periodically define new practice guidelines for medical physics practice to help advance the science of medical physics and to improve the quality of service to patients throughout the United States. Existing medical physics practice guidelines will be reviewed for the purpose of revision or renewal, as appropriate, on their fifth anniversary or sooner.Each medical physics practice guideline represents a policy statement by the AAPM, has undergone a thorough consensus process in which it has been subjected to extensive review, and requires the approval of the Professional Council. The medical physics practice guidelines recognize that the safe and effective use of diagnostic and therapeutic radiology requires specific training, skills, and techniques, as described in each document. Reproduction or modification of the published practice guidelines and technical standards by those entities not providing these services is not authorized.The following terms are used in the AAPM practice guidelines:Must and Must Not: Used to indicate that adherence to the recommendation is considered necessary to conform to this practice guideline.Should and Should Not: Used to indicate a prudent practice to which exceptions may occasionally be made in appropriate circumstances.

Influence of patient's physiologic factors and immobilization choice with stereotactic body radiotherapy for upper lung tumors.

The purpose of the present study was to compare the impact of pulmonary function, body habitus, and stereotactic body radiation therapy (SBRT) immobilization on setup and reproducibility for upper lung tumor. From 2008 through 2011, our institution's prospective SBRT database was searched for patients with upper lung tumors. Two SBRT immobilization strategies were used: full-length BodyFIX and thermoplastic S-frame. At simulation, free-breathing, four-dimensional computed tomography was performed. For each treatment, patients were set up to isocenter with in-room lasers and skin tattoos. Shifts from initial and subsequent couch positions with cone-beam computed tomography (CBCT) were analyzed. Accounting for setup uncertainties, institutional tolerance of CBCT-based shifts for treatment was 2, 2, and 4 mm in left-right, anterior-posterior, and cranial-caudal directions, respectively; shifts exceeding these limits required reimaging. Each patient's pretreatment pulmonary function test was recorded. A multistep, multivariate linear regression model was performed to elucidate intervariable dependency for three-dimensional calculated couch shift parameters. BodyFIX was applied to 76 tumors and S-frame to 17 tumors. Of these tumors, 41 were non-small cell lung cancer and 15 were metastatic from other sites. Lesions measured < 1 (15%), 1.1 to 2 (50%), 2.1 to 3 (25%), and > 3 (11%) cm. Errors from first shifts of first fractions were significantly less with S-frame than BodyFIX (p < 0.001). No difference in local control (LC) was found between S-frame and BodyFIX (p = 0.35); two-year LC rate was 94%. Multivariate modeling confirmed that the ratio of forced expiratory volume in the first second of expiration to forced vital capacity, body habitus, and the immobilization device significantly impacted couch shift errors. For upper lung tumors, initial setup was more consistent with S-frame than BodyFIX, resulting in fewer CBCT scans. Patients with obese habitus and poor lung function had more SBRT setup uncertainty; however, outcome and probability for LC remained excellent.

Pituitary adenylyl cyclase-activating polypeptide receptor re-sensitization induces plastic changes in the dopaminergic phenotype in the mature avian retina.

Pituitary Adenylyl Cyclase-Activating Polypeptide (PACAP) is a neuroactive peptide present in the avian retina where it activates adenylyl cyclase (AC) since early in development via PACAP receptors. The synthesis of cAMP in response to PACAP is observed since embryonic day 8/9 (E8/9). After E12, signaling via PACAP receptors desensitizes, reaching very low levels in the mature tissue. We show here that chronic administration of PACAP in vitro desensitizes PACAP-induced cAMP accumulation, while the administration of the PACAP antagonist (PACAP 6-38) re-sensitizes PACAP receptor/cyclase system in vitro and in vivo. Moreover, a twofold increase in the number of tyrosine hydroxylase positive (TH⁺) cells is observed after in vivo injection of PACAP6-38. NURR1, a transcription factor associated with the differentiation of dopaminergic cells in the CNS, is present in the chick retina in all developmental stages studied. The presence of NURR1 positive cells in the mature tissue far exceeds the number of TH⁺ cells, suggesting that these NURR1-positive cells might have the potential to express the dopaminergic phenotype. Our data show that if PACAP signaling is increased in mature retinas, plastic changes in dopaminergic phenotype can be achieved.

Brain FNDC5/Irisin Expression in Patients and Mouse Models of Major Depression.

Major depressive disorder (MDD) is a major cause of disability in adults. MDD is both a comorbidity and a risk factor for Alzheimer's disease (AD), and regular physical exercise has been associated with reduced incidence and severity of MDD and AD. Irisin is an exercise-induced myokine derived from proteolytic processing of fibronectin type III domain-containing protein 5 (FNDC5). FNDC5/irisin is reduced in the brains of AD patients and mouse models. However, whether brain FNDC5/irisin expression is altered in depression remains elusive. Here, we investigate changes in fndc5 expression in postmortem brain tissue from MDD individuals and mouse models of depression. We found decreased fndc5 expression in the MDD prefrontal cortex, both with and without psychotic traits. We further demonstrate that the induction of depressive-like behavior in male mice by lipopolysaccharide decreased fndc5 expression in the frontal cortex, but not in the hippocampus. Conversely, chronic corticosterone administration increased fndc5 expression in the frontal cortex, but not in the hippocampus. Social isolation in mice did not result in altered fndc5 expression in either frontal cortex or hippocampus. Finally, fluoxetine, but not other antidepressants, increased fndc5 gene expression in the mouse frontal cortex. Results indicate a region-specific modulation of fndc5 in depressive-like behavior and by antidepressant in mice. Our finding of decreased prefrontal cortex fndc5 expression in MDD individuals differs from results in mice, highlighting the importance of carefully interpreting observations in mice. The reduction in fndc5 mRNA suggests that decreased central FNDC5/irisin could comprise a shared pathologic mechanism between MDD and AD.

Assessment of dose-volume histogram precision for five clinical systems.

PURPOSE: To investigate the dependency of dose-volume histogram (DVH) behavior and precision on underlying discretization using shapes and dose distributions with known analytical DVHs for five commercial DVH calculators. METHODS: DVHs and summary metrics were extracted from all five systems using synthetic cone and cylinder objects for which the true volume and DVH curves were known. Trends in the curves and metrics were explored by varying the underlying voxelization of the CT image, structure set, and dose grid as well by varying the geometry of the structure and direction of a linear dose gradient. Using synthetic structures allowed for comparison with ground truth DVH curves to assess their accuracy while an algorithm was additionally developed to assess the precision of each system. The precision was calculated with a novel algorithm that treats any "stair step" behavior in a DVH curve as an uncertainty band and calculates the width, characterized as a percent difference, of the band for various DVH metrics. The underlying voxelization was additionally changed and DVHs were extracted for two clinical examples. The details of how each system calculated DVHs were also investigated and tendencies in the calculated curves, metrics, and precision were related to choices made in the calculation methodology. RESULTS: Calculation methodology differences that had a noticeable impact on the DVH curves and summary metrics include supersampling beyond the input grids and interpretation of the superior and inferior ends of the structures. Among the systems studied, the median precision ranged from 0.902% to 3.22%, and interquartile ranges varied from 1.09% to 3.91%. CONCLUSIONS: Commercial dose-evaluation solutions can calculate different DVH curves, structure volume measures, and dose statistics for the same input data due to differences in their calculation methodologies. This study highlights the importance of understanding and investigating the DVH calculation when considering a new clinical system and when using more than one system for data transfer.

Electronic charting of radiation therapy planning and treatment: Report of Task Group 262.

While most Radiation Oncology clinics have adopted electronic charting in one form or another, no consensus document exists that provides guidelines for safe and effective use of the Radiation Oncology electronic medical records (RO-EMR). Task Group 262 was formed to provide these guidelines as well as to provide recommendations to vendors for improving electronic charting functionality in future. Guidelines are provided in the following areas: Implementation and training for the RO-EMR, acceptance testing and quality assurance (QA) of the RO-EMR, use of the RO-EMR as an information repository, use of the RO-EMR as a workflow manager, electronic charting for brachytherapy and nonstandard treatments, and information technology (IT) considerations associated with the RO-EMR. The report was based on a literature search by the task group, an extensive survey of task group members on their respective RO-EMR practices, an AAPM membership survey on electronic charting, as well as group consensus.

Cerebrospinal Fluid Neurotransmitters, Cytokines, and Chemokines in Alzheimer's and Lewy Body Diseases.

BACKGROUND: Alzheimer's disease (AD) and Lewy body disease (LBD) are complex neurodegenerative disorders that have been associated with brain inflammation and impaired neurotransmission. OBJECTIVE: We aimed to determine concentrations of multiple cytokines, chemokines, and neurotransmitters previously associated with brain inflammation and synapse function in cerebrospinal fluid (CSF) from AD and LBD patients. METHODS: We examined a panel of 50 analytes comprising neurotransmitters, cytokines, chemokines, and hormones in CSF in a cohort of patients diagnosed with mild cognitive impairment (MCI), AD, LBD, or non-demented controls (NDC). RESULTS: Among neurotransmitters, noradrenaline (NA) was increased in AD CSF, while homovanillic acid (HVA), a dopamine metabolite, was reduced in both AD and LBD CSF relative to NDC. Six cytokines/chemokines out of 30 investigated were reliably detected in CSF. CSF vascular endothelial growth factor (VEGF) was significantly reduced in LBD patients relative to NDC. CONCLUSIONS: CSF alterations in NA, HVA, and VEGF in AD and LBD may reflect pathogenic features of these disorders and provide tools for improved diagnosis. Future studies are warranted to replicate current findings in larger, multicenter cohorts.

Effect of processing and storage time on the vitamin C and lycopene contents of nectar of pink guava (Psidium guajava L.).

In this study, the effect of processing and storage time on the vitamin C and lycopene contents was evaluated. Guavas were washed, cut in quarters, blanched, pulped and the pulp pasteurized. The pulp was used for the production of nectar: guava pulp, sugar and water were mixed in 5:3:12 proportions, and the mixture was pasteurized, poured while hot into 125 mL glass jars, and cooled rapidly to 25 degrees C. The production of nectar from fresh guava reduced vitamin C, lycopene and titratable acidity, by contrast soluble solid and pH increased significant. Vitamin C content from 168.9 to 62.3 mg/(100 g fresh weight), and lycopene content from 3.55 to 1.35 mg/(100 g fresh weight) (p < 0.001 in both cases. After 240 days at 10.0 +/- 2 degrees C, no further statistically significant change in lycopene and soluble solid content was observed (p > 0.05). Storage time did affect vitamin C, pH, and titratable acidity content, vitamin C content fell by 89.3% to 6.67 mg/(100 g fresh weight) (p < 0.001). Based on this study, guava nectar storage at 10 degrees C retained 46% of the content of vitamin C for 120 days.

Phantom Verification of AAA and Acuros Dose Calculations for Lung Cancer: Do Tumor Size and Regression Matter?

PURPOSE: This study aimed to evaluate dose calculation accuracy for the Eclipse Analytical Anisotropic Algorithm (AAA) and Acuros XB algorithm for various lung tumor sizes and to investigate dosimetric changes associated with treatment of regressing tumors. METHODS AND MATERIALS: A water phantom with cylindrical cork inserts (lung surrogates) was fabricated. Large (202 cm3), medium (54 cm3), and small (3 cm3) solid water tumors were implanted within cork inserts. A plain cork insert was used to simulate a lung without a tumor. The cork inserts and tumors were cut along the long axis, and Gafchromic film was placed between the sections to measure dose distributions. Three-dimensional conformal plans were created using 6 MV and 10 MV beams, and volumetric modulated arc therapy plans were created using 6 MV beams for each tumor size. Doses were calculated using Eclipse AAA and Acuros XB. The measured and calculated dose distributions were compared for each tumor size and treatment algorithm. To simulate a regressing tumor, the original plans created for the large tumor were separately delivered to the phantom that contained a small, medium, or no tumor. The dosimetric effects were evaluated using gamma passing rates with a 2%/2 mm criterion and dose profile comparisons. RESULTS: Agreement between the measurements and AAA calculations decreased as tumor size decreased, but Acuros XB showed better agreement for all tumor sizes. The largest difference was observed for a 6 MV volumetric modulated arc therapy plan created to treat the smallest tumor. The gamma passing rate was 89.7% but that of Acuros was 99.5%. For the tumor regression evaluation, the gamma passing rates ranged from 53% to 99% for AAA. For Acuros XB, the gamma passing rates were >98% for all scenarios. CONCLUSION: Both AAA and Acuros XB calculated the dose accurately for the largest lung tumor. For the smallest and regressing tumors, Acuros XB more accurately modelled the dose distribution compared with AAA.

Crosstalk between endoplasmic reticulum stress and brain inflammation in Alzheimer's disease.

While most often noted for its cognitive symptoms, Alzheimer's disease (AD) is, at its core, a disease of protein misfolding/aggregation, with an intriguing inflammatory component. Defective clearance and/or abnormal production of the amyloid-ß peptide (Aß), and its ensuing accumulation and aggregation, underlie two hallmark features of AD: brain accumulation of insoluble protein deposits known as amyloid or senile plaques, and buildup of soluble Aß oligomers (AßOs), diffusible toxins linked to synapse dysfunction and memory impairment. In neurons, as in typical eukaryotic cells, the endoplasmic reticulum (ER) serves as a main compartment for the folding, maturation, trafficking and quality control of newly synthesized proteins. The ER lumen, a calcium-rich, oxidizing environment, provides favorable conditions for these physiological functions to occur. These conditions, however, also favor protein aggregation. Several stressors, including metabolic/nutrient stress and certain pathologies, may upset the ER homeostasis, e.g., by affecting calcium levels or by causing the accumulation of unfolded or misfolded proteins. Whatever the underlying cause, the result is what is commonly known as "ER stress". This, in turn, triggers a conserved cellular response mechanism known as the "unfolded protein response" (UPR). The UPR comprises three pathways involving transcriptional or translational regulators aimed at normalizing ER function, and each of them results in pro-inflammatory signaling. A positive feedback loop exists between ER stress and inflammation, with clear implications for neurodegeneration and AD. Here, we explore recent findings on the role of ER stress and the UPR in inflammatory processes leading to synapse failure and memory impairment in AD. This article is part of the Special Issue entitled 'Metabolic Impairment as Risk Factors for Neurodegenerative Disorders.'

Design and clinical use of a rotational phantom for dosimetric verification of IMRT/VMAT treatments.

PURPOSE: To describe the design and clinical use of a rotational phantom for dosimetric verification of IMRT/VMAT treatment plans using radiochromic film. METHODS: A solid water cylindrical phantom was designed with separable upper and lower halves and rests on plastic bearings allowing for 360° rotation about its central axis. The phantom accommodates a half sheet of radiochromic film, and by rotating the cylinder, the film can be placed in any plane between coronal and sagittal. Calculated dose planes coinciding with rotated film measurements are exported by rotating the CT image and dose distribution within the treatment planning system. The process is illustrated with 2 rotated film measurements of an SRS treatment plan involving 4 separate targets. Additionally, 276 patient specific QA measurements were obtained with the phantom and analyzed with a 2%/2 mm gamma criterion. RESULTS: The average 2%/2 mm gamma passing rate for all 276 plans was 99.3%. Seventy-two of the 276 plans were measured with the plane of the film rotated between the coronal and sagittal planes and had an average passing rate of 99.4%. CONCLUSIONS: The rotational phantom allows for accurate film measurements in any plane. With this technique, regions of a dose distribution which might otherwise require multiple sagittal or coronal measurements can be verified with as few as a single measurement. This increases efficiency and, in combination with the high spatial resolution inherent to film dosimetry, makes the rotational technique an attractive option for patient-specific QA.

Image-guided radiotherapy quality control: Statistical process control using image similarity metrics.

PURPOSE: The purpose of this study was to demonstrate an objective quality control framework for the image review process. METHODS AND MATERIALS: A total of 927 cone-beam computed tomography (CBCT) registrations were retrospectively analyzed for 33 bilateral head and neck cancer patients who received definitive radiotherapy. Two registration tracking volumes (RTVs) - cervical spine (C-spine) and mandible - were defined, within which a similarity metric was calculated and used as a registration quality tracking metric over the course of treatment. First, sensitivity to large misregistrations was analyzed for normalized cross-correlation (NCC) and mutual information (MI) in the context of statistical analysis. The distribution of metrics was obtained for displacements that varied according to a normal distribution with standard deviation of σ = 2 mm, and the detectability of displacements greater than 5 mm was investigated. Then, similarity metric control charts were created using a statistical process control (SPC) framework to objectively monitor the image registration and review process. Patient-specific control charts were created using NCC values from the first five fractions to set a patient-specific process capability limit. Population control charts were created using the average of the first five NCC values for all patients in the study. For each patient, the similarity metrics were calculated as a function of unidirectional translation, referred to as the effective displacement. Patient-specific action limits corresponding to 5 mm effective displacements were defined. Furthermore, effective displacements of the ten registrations with the lowest similarity metrics were compared with a three dimensional (3DoF) couch displacement required to align the anatomical landmarks. RESULTS: Normalized cross-correlation identified suboptimal registrations more effectively than MI within the framework of SPC. Deviations greater than 5 mm were detected at 2.8σ and 2.1σ from the mean for NCC and MI, respectively. Patient-specific control charts using NCC evaluated daily variation and identified statistically significant deviations. This study also showed that subjective evaluations of the images were not always consistent. Population control charts identified a patient whose tracking metrics were significantly lower than those of other patients. The patient-specific action limits identified registrations that warranted immediate evaluation by an expert. When effective displacements in the anterior-posterior direction were compared to 3DoF couch displacements, the agreement was ±1 mm for seven of 10 patients for both C-spine and mandible RTVs. CONCLUSIONS: Qualitative review alone of IGRT images can result in inconsistent feedback to the IGRT process. Registration tracking using NCC objectively identifies statistically significant deviations. When used in conjunction with the current image review process, this tool can assist in improving the safety and consistency of the IGRT process.