Kenneth J Niermann

Vanderbilt University, Нашвилл, Michigan, United States

Are you Kenneth J Niermann?

Claim your profile

Publications (45)127.47 Total impact

  • International Journal of Radiation OncologyBiologyPhysics 10/2013; 87(2):S271. DOI:10.1016/j.ijrobp.2013.06.706 · 4.18 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Image segmentation has become a vital and often rate-limiting step in modern radiotherapy treatment planning. In recent years, the pace and scope of algorithm development, and even introduction into the clinic, have far exceeded evaluative studies. In this work we build upon our previous evaluation of a registration driven segmentation algorithm in the context of 8 expert raters and 20 patients who underwent radiotherapy for large space-occupying tumours in the brain. In this work we tested four hypotheses concerning the impact of manual segmentation editing in a randomized single-blinded study. We tested these hypotheses on the normal structures of the brainstem, optic chiasm, eyes and optic nerves using the Dice similarity coefficient, volume, and signed Euclidean distance error to evaluate the impact of editing on inter-rater variance and accuracy. Accuracy analyses relied on two simulated ground truth estimation methods: simultaneous truth and performance level estimation and a novel implementation of probability maps. The experts were presented with automatic, their own, and their peers' segmentations from our previous study to edit. We found, independent of source, editing reduced inter-rater variance while maintaining or improving accuracy and improving efficiency with at least 60% reduction in contouring time. In areas where raters performed poorly contouring from scratch, editing of the automatic segmentations reduced the prevalence of total anatomical miss from approximately 16% to 8% of the total slices contained within the ground truth estimations. These findings suggest that contour editing could be useful for consensus building such as in developing delineation standards, and that both automated methods and even perhaps less sophisticated atlases could improve efficiency, inter-rater variance, and accuracy.
    Physics in Medicine and Biology 05/2013; 58(12):4071-4097. DOI:10.1088/0031-9155/58/12/4071 · 2.92 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose: Episcleral eye plaque brachytherapy has been utilized in the treatment of intra-ocular malignancies, delivering large prescription doses to the apex of the tumor. Advances in dose calculation and image guidance, via calibrated fundus images, enable localization of the tumor and determination of dose to the macula, optic disc, and lens. A two-year post-implant study aims to correlate dosimetry with local tumor control and changes in visual acuity, as well as assess the need for plaque optimization with respect to critical structures. Methods: A retrospective, two-year follow-up study of 21 patients who have received episcleral eye plaque brachytherapy at our institution was used to correlate dosimetry with clinical outcomes and evaluate the need for eye plaque optimization. BEBIG Plaque Simulator wasused in treatment planning; fundus photographs were registered for tumor localization and the TG43-U1 formulism enabled dose calculation of I-125- loaded COMS plaques. Doses to the apex, macula, and optic disc were correlated to changes in apex height and visual acuity. Selected patients were replanned using optimization strategies to reduce dose to critical structures. Results: A total of seven patients (33%) noted improved eyesight at two years. 11 (52%) patients lost at least two lines of vision at two years. Two patients saw increases in apical height (9%) within two years. Optimized eye plaque plans were able to reduce optic disc and macular doses (average 68Gy and 80Gy, respectively) by 36% and 25% on the average, while maintaining the prescribed dose. Conclusion: Image guidance and optimization are important tools that can aid in treatment of intra-ocular malignancies, as these techniques provide physicists with the ability to spare critical structures while delivering the prescription dose, thus increasing the possibility of local control and vision sparing.
    Medical Physics 06/2012; 39(6):3803. DOI:10.1118/1.4735518 · 3.01 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Automatic segmentation of parotid glands in head and neck CT images for IMRT planning has drawn attention in recent years. Although previous approaches have achieved substantial success by reaching high overall volume-wise accuracy, suboptimal segmentations are observed on the interior boundary of the gland where the contrast is poor against the adjacent muscle groups. Herein we propose to use a constrained active shape model with landmark uncertainty to improve the segmentation in this area. Results obtained using this method are compared with results obtained using a regular active shape model through a leave-one-out experiment.
    Proceedings of SPIE - The International Society for Optical Engineering 02/2012; DOI:10.1117/12.911534 · 0.20 Impact Factor
  • Source
    A Chen, K J Niermann, M A Deeley, B M Dawant
    [Show abstract] [Hide abstract]
    ABSTRACT: Segmenting the thyroid gland in head and neck CT images is of vital clinical significance in designing intensity-modulated radiation therapy (IMRT) treatment plans. In this work, we evaluate and compare several multiple-atlas-based methods to segment this structure. Using the most robust method, we generate automatic segmentations for the thyroid gland and study their clinical applicability. The various methods we evaluate range from selecting a single atlas based on one of three similarity measures, to combining the segmentation results obtained with several atlases and weighting their contribution using techniques including a simple majority vote rule, a technique called STAPLE that is widely used in the medical imaging literature, and the similarity between the atlas and the volume to be segmented. We show that the best results are obtained when several atlases are combined and their contributions are weighted with a measure of similarity between each atlas and the volume to be segmented. We also show that with our data set, STAPLE does not always lead to the best results. Automatic segmentations generated by the combination method using the correlation coefficient (CC) between the deformed atlas and the patient volume, which is the most accurate and robust method we evaluated, are presented to a physician as 2D contours and modified to meet clinical requirements. It is shown that about 40% of the contours of the left thyroid and about 42% of the right thyroid can be used directly. An additional 21% on the left and 24% on the right require only minimal modification. The amount and the location of the modifications are qualitatively and quantitatively assessed. We demonstrate that, although challenged by large inter-subject anatomical discrepancy, atlas-based segmentation of the thyroid gland in IMRT CT images is feasible by involving multiple atlases. The results show that a weighted combination of segmentations by atlases using the CC as the similarity measure slightly outperforms standard combination methods, e.g. the majority vote rule and STAPLE, as well as methods selecting a single most similar atlas. The results we have obtained suggest that using our contours as initial contours to be edited has clinical value.
    Physics in Medicine and Biology 11/2011; 57(1):93-111. DOI:10.1088/0031-9155/57/1/93 · 2.92 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The purpose of this work was to characterize expert variation in segmentation of intracranial structures pertinent to radiation therapy, and to assess a registration-driven atlas-based segmentation algorithm in that context. Eight experts were recruited to segment the brainstem, optic chiasm, optic nerves, and eyes, of 20 patients who underwent therapy for large space-occupying tumors. Performance variability was assessed through three geometric measures: volume, Dice similarity coefficient, and Euclidean distance. In addition, two simulated ground truth segmentations were calculated via the simultaneous truth and performance level estimation algorithm and a novel application of probability maps. The experts and automatic system were found to generate structures of similar volume, though the experts exhibited higher variation with respect to tubular structures. No difference was found between the mean Dice similarity coefficient (DSC) of the automatic and expert delineations as a group at a 5% significance level over all cases and organs. The larger structures of the brainstem and eyes exhibited mean DSC of approximately 0.8-0.9, whereas the tubular chiasm and nerves were lower, approximately 0.4-0.5. Similarly low DSCs have been reported previously without the context of several experts and patient volumes. This study, however, provides evidence that experts are similarly challenged. The average maximum distances (maximum inside, maximum outside) from a simulated ground truth ranged from (-4.3, +5.4) mm for the automatic system to (-3.9, +7.5) mm for the experts considered as a group. Over all the structures in a rank of true positive rates at a 2 mm threshold from the simulated ground truth, the automatic system ranked second of the nine raters. This work underscores the need for large scale studies utilizing statistically robust numbers of patients and experts in evaluating quality of automatic algorithms.
    Physics in Medicine and Biology 07/2011; 56(14):4557-77. DOI:10.1088/0031-9155/56/14/021 · 2.92 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To determine whether MLN8054, an Aurora kinase A (Aurora-A) inhibitor causes radiosensitization in androgen-insensitive prostate cancer cells in vitro and in vivo. In vitro studies consisted of culturing PC3 and DU145 prostate cancer cells and then immunoblotting Aurora A and phospho-Aurora A after radiation and/or nocodazole with MLN8054. Phases of the cell cycle were measured with flow cytometry. PC3 and DU145 cell lines were measured for survival after treatment with MLN8054 and radiation. Immunofluorescence measured γ-H2AX in the PC3 and DU145 cells after treatment. In vivo studies looked at growth delay of PC3 tumor cells in athymic nude mice. PC3 cells grew for 6 to 8 days in mice treated with radiation, MLN8054, or combined for 7 more days. Tumors were resected and fixed on paraffin and stained for von Willebrand factor, Ki67, and caspase-3. In vitro inhibition of Aurora-A by MLN8054 sensitized prostate cancer cells, as determined by dose enhancement ratios in clonogenic assays. These effects were associated with sustained DNA double-strand breaks, as evidenced by increased immunofluorescence for γ-H2AX and significant G2/M accumulation and polyploidy. In vivo, the addition of MLN8054 (30 mg/kg/day) to radiation in mouse prostate cancer xenografts (PC3 cells) significantly increased tumor growth delay and apoptosis (caspase-3 staining), with reduction in cell proliferation (Ki67 staining) and vascular density (von Willebrand factor staining). MLN8054, a novel small molecule Aurora-A inhibitor showed radiation sensitization in androgen-insensitive prostate cancer in vitro and in vivo. This warrants the clinical development of MLN8054 with radiation for prostate cancer patients.
    International journal of radiation oncology, biology, physics 07/2011; 80(4):1189-97. DOI:10.1016/j.ijrobp.2011.01.060 · 4.18 Impact Factor
  • Radiotherapy and Oncology 05/2011; 99. DOI:10.1016/S0167-8140(11)71154-9 · 4.86 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Aurora kinase B (AURKB) is critical to the process of mitosis, aiding in chromosome condensation by phosphorylating histone H3. We investigated the effects of AZD1152, an AURKB inhibitor, on radiosensitivity of androgen-insensitive prostate cancer cells. The goal of this study was to test whether AZD1152 increases the susceptibility of hormone-refractory prostate cancer cells to radiation-induced DNA damage and to determine the conditions of AZD1152 treatment that maximize radiosensitization. PC3 and DU145 cells were treated with various AZD1152 doses for various durations to elucidate the conditions that yielded maximal increases in G(2)/M-phase and polyploid cells. To assess DNA damage, γ-H2AX phosphorylation was quantified for cells grown under radiosensitizing conditions and subjected to either no radiation or 5 Gy radiation. Radiosensitivity was determined by clonogenic assays. Cell cycle effects in both cell lines were maximized by treatment with 60 nM AZD1152 for 48 h. AZD1152-treated cells exhibited significantly increased DNA damage 30 min postirradiation (PC3: 100% compared to 68%, P  =  0.035; DU145: 100% compared to 69%, P  =  0.034), with additional DNA damage 6 h postirradiation (PC3: 85% compared to 15%, P  =  0.002; DU145: 67% compared to 21%, P  =  0.012). Radiosensitivity was increased in both cell lines, with dose enhancement ratios of 1.53 for PC3 cells (P  =  0.017) and 1.71 for DU145 cells (P  =  0.02). This study identifies the optimal AZD1152 treatment conditions to maximize the radiosensitization of PC3 and DU145 cells. These results suggest a major role for DNA damage and impairment of DNA repair mechanisms in AZD1152-induced radiosensitization of prostate cancer cells.
    Radiation Research 04/2011; 175(4):444-51. DOI:10.1667/RR2317.1 · 2.45 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Segmenting the thyroid gland in head and neck CT images for IMRT treatment planning is of great importance. In this work, we evaluate and compare multi-atlas methods to segment this structure. The various methods we evaluate range from using a single average atlas representative of the population to selecting one atlas based on three similarity measures. We also compare ways to combine segmentation results obtained with several atlases, i.e., vote rule, and STAPLE, which is a commonly used method to combine multiple segmentations. We show that the best results are obtained when several atlases are combined. We also show that with our data sets, STAPLE does not lead to the best results.
    Proceedings of SPIE - The International Society for Optical Engineering 03/2011; DOI:10.1117/12.878246 · 0.20 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Despite advances in treatment, cancer remains the 2nd most common cause of death in the United States. Poor cure rates may result from the ability of cancer to recur and spread after initial therapies have seemingly eliminated detectable signs of disease. A growing body of evidence supports a role for cancer stem cells (CSCs) in tumor regrowth and spread after initial treatment. Thus, targeting CSCs in combination with traditional induction therapies may improve treatment outcomes and survival rates. Unfortunately, CSCs tend to be resistant to chemo- and radiation therapy, and a better understanding of the mechanisms underlying CSC resistance to treatment is necessary. This paper provides an update on evidence that supports a fundamental role for CSCs in cancer progression, summarizes potential mechanisms of CSC resistance to treatment, and discusses classes of drugs currently in preclinical or clinical testing that show promise at targeting CSCs.
    Journal of Oncology 01/2011; 2011(12):941876. DOI:10.1155/2011/941876
  • Medical Physics 01/2011; 38(6):3624-. DOI:10.1118/1.3612551 · 3.01 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Intensity-modulated radiation therapy (IMRT) is the state of the art technique for head and neck cancer treatment. It requires precise delineation of the target to be treated and structures to be spared, which is currently done manually. The process is a time-consuming task of which the delineation of lymph node regions is often the longest step. Atlas-based delineation has been proposed as an alternative, but, in the authors' experience, this approach is not accurate enough for routine clinical use. Here, the authors improve atlas-based segmentation results obtained for level II-IV lymph node regions using an active shape model (ASM) approach. An average image volume was first created from a set of head and neck patient images with minimally enlarged nodes. The average image volume was then registered using affine, global, and local nonrigid transformations to the other volumes to establish a correspondence between surface points in the atlas and surface points in each of the other volumes. Once the correspondence was established, the ASMs were created for each node level. The models were then used to first constrain the results obtained with an atlas-based approach and then to iteratively refine the solution. The method was evaluated through a leave-one-out experiment. The ASM- and atlas-based segmentations were compared to manual delineations via the Dice similarity coefficient (DSC) for volume overlap and the Euclidean distance between manual and automatic 3D surfaces. The mean DSC value obtained with the ASM-based approach is 10.7% higher than with the atlas-based approach; the mean and median surface errors were decreased by 13.6% and 12.0%, respectively. The ASM approach is effective in reducing segmentation errors in areas of low CT contrast where purely atlas-based methods are challenged. Statistical analysis shows that the improvements brought by this approach are significant.
    Medical Physics 12/2010; 37(12):6338-46. DOI:10.1118/1.3515459 · 3.01 Impact Factor
  • Medical Physics 06/2010; 37(6). DOI:10.1118/1.3469067 · 3.01 Impact Factor
  • Medical Physics 06/2010; 37(6). DOI:10.1118/1.3468132 · 3.01 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Segmenting the lymph node regions in head and neck CT images has been a challenging topic in the area of medical image segmentation. The method proposed herein implements an atlas-based technique constrained by an active shape model (ASM) to segment the level II, III and IV lymph nodes as one structure. A leave-one-out evaluation study performed on 15 data sets shows that the results obtained with this technique are better than those obtained with a pure atlas-based segmentation method, in particular in regions of poor contrast.
    Proceedings of SPIE - The International Society for Optical Engineering 03/2010; DOI:10.1117/12.843823 · 0.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The advent of antiangiogenic drugs in cancer therapy necessitates an imaging modality that can longitudinally assess posttreatment changes in tumor vasculature. In this regard, microbubble contrast-enhanced ultrasonography (CEUS) offers several advantages over conventional imaging modalities. The small size of microbubbles (approximately 2-3 mum) permits their retention in the intravascular compartment and travel through the tortuous tumor vasculature. Mathematical models applied to signal intensity versus time depicting the kinetics of microbubble flow through the tumor are used to characterize tumor vascular density, blood flow velocity, and perfusion. In vivo studies using CEUS have demonstrated its comparability to dynamic contrast-enhanced magnetic resonance imaging and fluorodeoxyglucose positron emission tomography in distinguishing between diseased or malignant tissue and normal tissue. Moreover, CEUS has great potential for other novel clinical applications such as improved cancer diagnosis, enhanced medication delivery, and early antiangiogenic cancer treatment response evaluation. This review discusses the principles and potential clinical applications of CEUS in determining tumor response and its promising role in enhancing medication delivery in certain tumors.
    Ultrasound quarterly 12/2009; 25(4):175-83. DOI:10.1097/RUQ.0b013e3181bce364 · 1.40 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Angiogenesis has generated interest in oncology because of its important role in cancer growth and progression, particularly when combined with cytotoxic therapies, such as radiotherapy. Among the numerous pathways influencing vascular growth and stability, inhibition of protein kinase B(Akt) or protein kinase C(PKC) can influence tumor blood vessels within tumor microvasculature. Therefore, we wanted to determine whether PKC inhibition could sensitize lung tumors to radiation. The combination of the selective PKCbeta inhibitor Enzastaurin (ENZ, LY317615) and ionizing radiation were used in cell culture and a mouse model of lung cancer. Lung cancer cell lines and human umbilical vascular endothelial cells (HUVEC) were examined using immunoblotting, cytotoxic assays including cell proliferation and clonogenic assays, and Matrigel endothelial tubule formation. In vivo, H460 lung cancer xenografts were examined for tumor vasculature and proliferation using immunohistochemistry. ENZ effectively radiosensitizes HUVEC within in vitro models. Furthermore, concurrent ENZ treatment of lung cancer xenografts enhanced radiation-induced destruction of tumor vasculature and proliferation by IHC. However, tumor growth delay was not enhanced with combination treatment compared with either treatment alone. Analysis of downstream effectors revealed that HUVEC and the lung cancer cell lines differed in their response to ENZ and radiation such that only HUVEC demonstrate phosphorylated S6 suppression, which is downstream of mTOR. When ENZ was combined with the mTOR inhibitor, rapamycin, in H460 lung cancer cells, radiosensitization was observed. PKC appears to be crucial for angiogenesis, and its inhibition by ENZ has potential to enhance radiotherapy in vivo.
    International journal of radiation oncology, biology, physics 11/2009; 77(5):1518-26. DOI:10.1016/j.ijrobp.2009.06.044 · 4.18 Impact Factor
  • International Journal of Radiation OncologyBiologyPhysics 09/2008; 72(1). DOI:10.1016/j.ijrobp.2008.06.955 · 4.18 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To determine the efficacy of combining radiation (XRT) with a dual epidermal growth factor receptor (EGFR)/vascular endothelial growth factor receptor inhibitor, AEE788, in prostate cancer models with different levels of EGFR expression. Immunoblotting was performed for EGFR, phosphorylated-EGFR, and phosphorylated-AKT in prostate cancer cells. Clonogenic assays were performed on DU145, PC-3, and human umbilical vein endothelial cells treated with XRT +/- AEE788. Tumor xenografts were established for DU145 and PC-3 on hind limbs of athymic nude mice assigned to four treatment groups: (1) control, (2) AEE788, (3) XRT, and (4) AEE788 + XRT. Tumor blood flow and growth measurements were performed using immunohistochemistry and imaging. AEE788 effectively decreased phosphorylated-EGFR and phosphorylated-AKT levels in DU145 and PC-3 cells. Clonogenic assays showed no radiosensitization for DU145 and PC-3 colonies treated with AEE788 + XRT. However, AEE788 caused decreased proliferation in DU145 cells. AEE788 showed a radiosensitization effect in human umbilical vein endothelial cells and increased apoptosis susceptibility. Concurrent AEE788 + XRT compared with either alone led to significant tumor growth delay in DU145 tumors. Conversely, PC-3 tumors derived no added benefit from combined-modality therapy. In DU145 tumors, a significant decrease in tumor blood flow with combination therapy was shown by using power Doppler sonography and tumor blood vessel destruction on immunohistochemistry. Maldi-spectrometry (MS) imaging showed that AEE788 is bioavailable and heterogeneously distributed in DU145 tumors undergoing therapy. AEE788 + XRT showed efficacy in vitro/in vivo with DU145-based cell models, whereas PC-3-based models were adequately treated with XRT alone without added benefit from combination therapy. These findings correlated with differences in EGFR expression and showed effects on both tumor cell proliferation and vascular destruction.
    International Journal of Radiation OncologyBiologyPhysics 06/2008; 71(1):237-46. DOI:10.1016/j.ijrobp.2007.12.049 · 4.18 Impact Factor

Publication Stats

603 Citations
127.47 Total Impact Points

Institutions

  • 2005–2013
    • Vanderbilt University
      • • Department of Radiation Oncology
      • • Vanderbilt-Ingram Cancer Center (VICC)
      Нашвилл, Michigan, United States
  • 2007–2011
    • Gateway-Vanderbilt Cancer Treatment Center
      Clarksville, Tennessee, United States