Kenneth J Niermann

Gateway-Vanderbilt Cancer Treatment Center, Clarksville, Tennessee, United States

Are you Kenneth J Niermann?

Claim your profile

Publications (37)92.71 Total impact

  • A. Chen · K.J. Niermann · M.A. Deeley · B.M. Dawant

    No preview · Article · Apr 2012
  • [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.
    No preview · Article · Feb 2012 · Proceedings of SPIE - The International Society for Optical Engineering
  • 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.
    Full-text · Article · Nov 2011 · Physics in Medicine and Biology
  • [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.
    No preview · Article · Jul 2011 · International journal of radiation oncology, biology, physics
  • 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.
    Full-text · Article · Apr 2011 · Radiation Research
  • Antong Chen · Kenneth J. Niermann · Matthew A. Deeley · Benoit M. Dawant
    [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.
    No preview · Article · Mar 2011 · Proceedings of SPIE - The International Society for Optical Engineering
  • 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.
    Full-text · Article · Jan 2011 · Journal of Oncology
  • 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.
    Full-text · Article · Dec 2010 · Medical Physics
  • [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.
    No preview · Article · Mar 2010 · Proceedings of SPIE - The International Society for Optical Engineering
  • Misun Hwang · Kenneth J Niermann · Andrej Lyshchik · Arthur C Fleischer
    [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.
    No preview · Article · Dec 2009 · Ultrasound quarterly
  • [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.
    No preview · Article · Nov 2009 · International journal of radiation oncology, biology, physics
  • L. Moretti · K. W. Kim · K. J. Niermann · B. Lu

    No preview · Conference Paper · Sep 2008
  • K. J. Niermann · E. S. Yang · H. Wang · G. Jiang · D. E. Hallahan · F. Xia

    No preview · Article · Sep 2008 · International Journal of Radiation OncologyBiologyPhysics
  • 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.
    Full-text · Article · Jun 2008 · International Journal of Radiation OncologyBiologyPhysics
  • K. J. Niermann · D. Xiao · C. D. Willey · T. Tu · B. Lu

    No preview · Article · Nov 2007 · International Journal of Radiation OncologyBiologyPhysics
  • [Show abstract] [Hide abstract]
    ABSTRACT: The purpose of this study was to evaluate the ability of dynamic microbubble contrast-enhanced sonography (MCES), in comparison with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET), to quantitatively characterize tumor perfusion in implanted murine tumors before and after treatment with a variety of regimens. Seventeen mice with Lewis lung carcinoma implants were categorized to control, radiation therapy alone, antiangiogenic chemotherapy alone, and combined chemoradiation. On day 0 of each treatment regimen, MCES and DCE-MRI of each tumor were performed. On day 5 of treatment, dynamic FDG-PET, MCES, and DCE-MRI were performed. Microbubble contrast-enhanced sonography showed that intratumoral perfusion, blood volume, and blood velocity were highest in the untreated control group and successively lower in each of the treatment groups: radiation therapy alone resulted in a two-thirds reduction of perfusion; antiangiogenic chemotherapy resulted in a relatively larger reduction; and combined chemoradiotherapy resulted in the largest reduction. Microbubble contrast-enhanced sonography revealed longitudinal decreases in tumor perfusion, blood volume, and microvascular velocity over the 5-day course of chemoradiotherapy (all P < .01); conversely, these values rose significantly for the untreated control tumors (P < .01). Dynamic contrast-enhanced MRI showed a smaller and statistically insignificant average decrease in relative tumor perfusion for treated tumors. Dynamic PET revealed delayed uptake of FDG in the tumors that underwent chemoradiotherapy. Microbubble contrast-enhanced sonography is an effective tool in the noninvasive, quantitative, longitudinal characterization of neovascularization in murine tumor models and is correlative with DCE-MRI and FDG-PET. Microbubble contrast-enhanced sonography has considerable potential in the clinical assessment of tumor neovascularization and in the assessment of the response to treatment.
    No preview · Article · Jun 2007 · Journal of ultrasound in medicine: official journal of the American Institute of Ultrasound in Medicine
  • Source
    Luigi Moretti · Yong I Cha · Kenneth John Niermann · Bo Lu
    [Show abstract] [Hide abstract]
    ABSTRACT: The induction of cell death by radiation has largely been attributed to pro-apoptotic mechanisms. Autophagy, an alternative form of programmed cell death, has recently been shown to contribute significantly to anti-neoplastic effects of radiation therapy. In light of this, ER stress has been shown to trigger both apoptosis and autophagy, and act as an important mediator linking the two programmed cell death pathways. Recent data reveal that ER stress leads to activation of autophagosome formation with LC3 conversion via either PERK-eIF2a pathway or IRE1-JNK pathway. In this focused review, we summarize the main molecular mediators that control cellular "switches" between apoptosis and autophagy pathways by utilizing radiation therapy as a model.
    Preview · Article · May 2007 · Cell cycle (Georgetown, Tex.)
  • [Show abstract] [Hide abstract]
    ABSTRACT: Delineating critical structures for radiotherapy of the brain is required for advanced radiotherapy technologies to determine if the dose from the proposed treatment will impair the functionality of the structures. Employing an automatic segmentation computer module in the radiation oncology treatment planning process has the potential to significantly increase the efficiency, cost-effectiveness, and, ultimately, clinical outcome of patients undergoing radiation therapy. In earlier work, we have shown that atlas-based segmentation of large structures such as the brainstem or the cerebellum was an achievable objective. We have also shown that smaller structures such as the optic nerves or optic chiasm were more difficult to segment automatically. In this work, we present an extension to this approach in which atlas-based segmentation is followed by a series of additional steps. We show that this new approach substantially improves our previous results. We also show that we can segment CT images alone when we previously relied on a combination of MR and CT images.
    No preview · Article · Mar 2007 · Proceedings of SPIE - The International Society for Optical Engineering
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The objective of this study was to assess changes in the water apparent diffusion coefficient (ADC) and in pharmacokinetic parameters obtained from the fast-exchange regime (FXR) modeling of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) during neoadjuvant chemotherapy in breast cancer. Eleven patients with locally advanced breast cancer underwent MRI examination prior to and after chemotherapy but prior to surgery. A 1.5-T scanner was used to obtain T1, ADC and DCE-MRI data. DCE-MRI data were analyzed by the FXR model returning estimates of K(trans) (volume transfer constant), v(e) (extravascular extracellular volume fraction) and tau(i) (average intracellular water lifetime). Histogram and correlation analyses assessed parameter changes post-treatment. Significant (P < .05) changes or trends towards significance (P < .10) were seen in all parameters except tau(i), although there was qualitative reduction in tau(i) values post-treatment. In particular, there was reduction (P < .035) in voxels with K(trans) values in the range 0.2-0.5 min(-1) and a decrease (P < .05) in voxels with ADC values in the range 0.99 x 10(-3) to 1.35 x 10(-3) mm2/s. ADC and v(e) were negatively correlated (r = -.60, P < .02). Parameters sensitive to water distribution and geometry (T(1), v(e), tau(i) and ADC) correlated with a multivariable linear regression model. The analysis presented here is sensitive to longitudinal changes in breast tumor status; K(trans) and ADC are most sensitive to these changes. Relationships between parameters provide information on water distribution and geometry in the tumor environment.
    Preview · Article · Feb 2007 · Magnetic Resonance Imaging
  • [Show abstract] [Hide abstract]
    ABSTRACT: Stereotactic radiotherapy (ablative radiation) is a modality that holds considerable promise for effective treatment of intracranial and extracranial malignancies. Although tumor vasculature is relatively resistant to small fractionated doses of ionizing radiation, large ablative doses of ionizing radiation lead to effective demise of the tumor vasculature. The purpose of this study was (1) to noninvasively monitor and compare tumor physiologic parameters in response to ablative radiation treatments and (2) to use these noninvasive parameters to optimize the schedule of administration of radiation therapy. Lewis lung carcinoma tumors were implanted into C57BL/6 mice and treated with ablative radiation. The kinetics of change in physiologic parameters of a response to single-dose 20-Gy treatments was measured. Parameters studied included tumor blood flow, apoptosis, and proliferation rates. Serial tumor sections were stained to correlate noninvasive Doppler assessment of tumor blood flow with microvasculature histologic findings. A single administration of 20 Gy led to an incomplete tumor vascular response, with subsequent recovery of tumor blood flow within 4 days after treatment. Sustained reduction of tumor blood flow by administering the successive ablative radiation treatment before tumor blood flow recovery led to a 3-fold tumor growth delay. The difference in tumor volumes at each measurement time point (every 2 days) was statistically significant (P=.016). This study suggests a rational design of schedule optimization for radiation-mediated, vasculature-directed treatments guided by noninvasive assessment of tumor blood flow levels to ultimately improve the tumor response.
    No preview · Article · Jan 2007 · Journal of ultrasound in medicine: official journal of the American Institute of Ultrasound in Medicine

Publication Stats

707 Citations
92.71 Total Impact Points


  • 2007-2012
    • Gateway-Vanderbilt Cancer Treatment Center
      Clarksville, Tennessee, United States
  • 2003-2011
    • Vanderbilt University
      • • Department of Radiation Oncology
      • • Vanderbilt Institute of Imaging Science
      • • Department of Radiology and Radiological Sciences
      Nashville, Michigan, United States