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This paper describes the first years of what became known as the Tomotherapy Research Group at the Department of Medical Physics at the University of Wisconsin-Madison (UW). The group's roots were in algorithm and software development for radiation therapy dose calculations. The concept of helical tomotherapy sprang from the design of a treatment unit which could make the computation easier which in turn created a treatment unit that created the capability to do image-guided radiotherapy. The paper discusses the genesis of our concepts and some of the difficulties encountered along the way.

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The small size of Arabidopsis provides both opportunities and difficulties for laboratory research. Large numbers of plants can be grown in a relatively small area making it easy to observe and investigate interesting phenotypes. Conversely, their small size can also make it difficult to obtain large quantities of tissue for investigation using modern molecular techniques. Sowing large numbers of their seed can overcome this; however, their small seed size makes this difficult. Here we present the Vacuum Seed Sowing Manifold (VSSM), a simple device that can be printed using a 3D printer and provides a new high throughput method to sow large numbers of seeds at a range of densities.

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BACKGROUND AND PURPOSE: To compare left-sided whole breast conventional and intensity-modulated radiotherapy (IMRT) treatment planning techniques. MATERIALS AND METHODS: Treatment plans were created for 10 consecutive patients. Three-dimensional conformal radiotherapy (3DCRT), forward-planned IMRT (for-IMRT), and inverse-planned IMRT (inv-IMRT) used two tangent beams. For-IMRT utilized up to four segments per beam. For helical tomotherapy (HT) plans, beamlet entrance and/or exit to critical structures was blocked. Topotherapy plans, which used static gantry angles with simultaneous couch translation and inverse-planned intensity modulation, used two tangent beams. Plans were normalized to 50Gy to 95% of the retracted PTV. RESULTS: Target max doses were reduced with for-IMRT compared to 3DCRT, which were further reduced with HT, topotherapy, and inv-IMRT. HT resulted in lowest heart and ipsilateral lung max doses, but had higher mean doses. Inv-IMRT and topotherapy reduced ipsilateral lung mean and max doses compared to 3DCRT and for-IMRT. CONCLUSIONS: All modalities evaluated provide adequate coverage of the intact breast. HT, topotherapy, and inv-IMRT can reduce high doses to the target and normal tissues, although HT results in increased low doses to large volume of normal tissue. For-IMRT improves target homogeneity compared with 3DCRT, but to a lesser degree than the inverse-planned modalities.

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The goal of radiation therapy is to eradicate tumor stem cells while sparing healthy tissue. Therefore, the first aim must be to delineate tumor from healthy tissue. Advanced imaging techniques will enable one to reduce the uncertainty of microscopic extension of disease. Ultimately, advanced functional imaging systems correlated with image-registered pathological specimens will allow one to delineate disease extent from normal tissue at the tumor periphery. When it is not possible to determine the CTV margin with reasonable certainty, the margins must remain generous and conformal avoidance methodology could and should be deployed to spare critical normal structures. Of equal importance to defining the CTV is the need to guarantee that this target is indeed treated. For this purpose, image guidance using a variety of systems including portal images, ultrasound devices, and CT scanners at the time of treatment has been implemented. Some image-guided methods, portal images for instance, are more amenable for use with rigid structures such as encountered in the sinus whereas others like ultrasound or CT scanners are able to account for nonrigid setup variations. Several strategies for preventing organ motion from degrading the precision that radiotherapy offers have been described. In particular, a CT scan at the time of treatment delivery can also be used as the basis to reconstruct the dose received by the patient. Dose reconstruction will allow the dose just delivered to be superimposed on the pretreatment CT scan and will allow one to compare the reconstructed delivered dose distribution with the planned dose distribution to assess discrepancies between these. Furthermore, reconstruction of the delivered dose distributions holds the promise of allowing one to accumulate dose delivered to the tumor and normal structures on a fraction per fraction basis. This will ultimately allow for the determination of treatment-specific tumor control probabilities and normal tissue complication probabilities.

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Since the beam width on the helical tomotherapy machine produced by TomoTherapy Inc., is typically a few centimeters in the longitudinal direction (into the bore), the optimizer must choose to have a relatively high intensity local to the inside edge of a tumor or planning treatment volume (PTV) when avoiding an immediately adjacent organ at risk (OAR), either superior or inferior. By using a standalone version of the TomoTherapy dose calculator, a realistic beam is applied to idealized deconvolution schemes including the MATLAB Optimizer Toolbox for a simple one-dimensional PTV with adjacent OARs. The results are compared to a clinical example on the TomoTherapy planning station. It is learned that a Gibbs phenomenon type of oscillation in the dose within the tumor under these special circumstances is not unique to TomoTherapy, but is related to the attempt to form a sharp dose gradient-sharper than the beam profile with typical optimization constraints set to achieve a uniform dose as close as possible to the prescription. The clinical implication is that the Gibbs-induced cold spots force the dose to increase in the PTV if a typical PTV dose-volume constraint is used. It is recommended that the dose prescription be smoothed prior to optimization or the dosimetric goals for an OAR adjacent to the PTV are such that a sharp dose falloff is not demanded, especially if the user reduces the requirements that such an OAR be of both high importance and immediately adjacent to the PTV edge.

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The previous theoretical work of a delivery transfer function (DTF) in radiotherapy is expanded to include the unique intensity modulation method of helical tomotherapy. In addition to the collimation of each beamlet, and the Gaussian scatter convolution spreading of the dose that other radiotherapy units have, helical tomotherapy uses 51 small arcs of varying lengths to adjust the intensity. The blurring from these arcs is not taken into account during treatment planning. A theoretical DTF is constructed, and a calculation is performed which includes this unique source motion in relation to the other DTF components. Various typical delivery parameters are used to generate resolution maps for a constant intensity projection. Near the isocenter, the transverse (to a given beam direction) blurring is small but at larger radii (>6 cm), the source blurring dominates over leaf size. For most clinical situations, this inherent source motion blurring is expected to be negligible.

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Image-guided IMRT is a revolutionary concept whose clinical implementation is rapidly evolving. Methods of executing beam intensity modulation have included individually designed compensators, static multi-leaf collimators (MLC), dynamic MLC, and sequential (serial) tomotherapy. We have developed helical tomotherapy as an innovative solution to overcome some of the limitations of other IMRT systems. The unique physical design of helical tomotherapy allows the realization of the concepts of adaptive radiotherapy and conformal avoidance. In principle, these advances should improve normal tissue sparing and permit dose reconstruction and verification, thereby allowing significant biologically effective dose escalation. Recent radiobiological findings can be translated into altered fractionation schemes that aim to improve the local control and long-term survival. This strategy is being tested at the University of Wisconsin using helical tomotherapy with its highly precise delivery and verification system along with meticulous and practical forms of immobilization. Innovative techniques such optical guidance, respiratory gating, and ultrasound assessments are being designed and tailored for helical tomotherapy use. The intrinsic capability of helical tomotherapy for megavoltage CT (MVCT) imaging for IMRT image-guidance is being optimized. The unique features of helical tomotherapy might allow implementation of image-guided IMRT that was previously impossible or impractical. Here we review the technological, physical, and radiobiological rationale for the ongoing and upcoming clinical trials that will use image-guided IMRT in the form of helical tomotherapy; and we describe our plans for testing our hypotheses in a rigorous prospective fashion.

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BACKGROUND: This study was designed to evaluate the integral dose (ID) received by normal tissue from intensity-modulated radiotherapy (IMRT) for prostate cancer. METHODS AND MATERIALS: Twenty-five radiation treatment plans including IMRT using a conventional linac with both 6 MV (6MV-IMRT) and 20 MV (20MV-IMRT), as well as three-dimensional conformal radiotherapy (3DCRT) using 6 MV (6MV-3DCRT) and 20 MV (20MV-3DCRT) and IMRT using tomotherapy (6MV) (Tomo-IMRT), were created for 5 patients with localized prostate cancer. The ID (mean dose x tissue volume) received by normal tissue (NTID) was calculated from dose-volume histograms. RESULTS: The 6MV-IMRT resulted in 5.0% lower NTID than 6MV-3DCRT; 20 MV beam plans resulted in 7.7%-11.2% lower NTID than 6MV-3DCRT. Tomo-IMRT NTID was comparable to 6MV-IMRT. Compared with 6MV-3DCRT, 6MV-IMRT reduced IDs to the rectal wall and penile bulb by 6.1% and 2.7%, respectively. Tomo-IMRT further reduced these IDs by 11.9% and 16.5%, respectively. The 20 MV did not reduce IDs to those structures. CONCLUSIONS: The difference in NTID between 3DCRT and IMRT is small. The 20 MV plans somewhat reduced NTID compared with 6 MV plans. The advantage of tomotherapy over conventional IMRT and 3DCRT for localized prostate cancer was demonstrated in regard to dose sparing of rectal wall and penile bulb while slightly decreasing NTID as compared with 6MV-3DCRT.

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PURPOSE: To evaluate the utility of relatively low-dose megavoltage computed tomography (MVCT) images from a clinical helical tomotherapy system for setup verification purposes. METHODS AND MATERIALS: Cross-sectional kilovolt computed tomography (kVCT) images were obtained for treatment planning purposes on a diagnostic third-generation CT scanner, followed by MVCT images from a helical tomotherapy system in 8 pet dogs with spontaneously occurring tumors. The kVCT and MVCT images were aligned for setup verification purposes, allowing repositioning before treatment delivery. RESULTS: Tumors are readily visualized on the MVCT images. At a dose of 2-3 cGy, the MVCT images are of sufficient quality for verification of treatment setup, but soft-tissue contrast is inferior to that with conventional kVCT. The MV and kVCT images were successfully aligned. When necessary, patients undergoing helical tomotherapy were repositioned before treatment. CONCLUSIONS: Megavoltage CT image quality is sufficient for tumor identification and three-dimensional setup verification in dogs with spontaneous tumors. The MVCT images can be aligned with the planning kVCT to ensure proper patient registration before treatment. Image alignment was successful in these canine patients, despite no skin markings defining patient positioning between the two scans. MVCT images facilitate setup verification, and their tomographic nature offers improvements over conventional portal imaging.

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PURPOSE: To review the state of the art in image-guided precision conformal radiotherapy and to describe how helical tomotherapy compares with the image-guided practices being developed for conventional radiotherapy. MATERIALS AND METHODS: Image guidance is beginning to be the fundamental basis for radiotherapy planning, delivery, and verification. Radiotherapy planning requires more precision in the extension and localization of disease. When greater precision is not possible, conformal avoidance methodology may be indicated whereby the margin of disease extension is generous, except where sensitive normal tissues exist. Radiotherapy delivery requires better precision in the definition of treatment volume, on a daily basis if necessary. Helical tomotherapy has been designed to use CT imaging technology to plan, deliver, and verify that the delivery has been carried out as planned. The image-guided processes of helical tomotherapy that enable this goal are described. RESULTS: Examples of the results of helical tomotherapy processes for image-guided intensity-modulated radiotherapy are presented. These processes include megavoltage CT acquisition, automated segmentation of CT images, dose reconstruction using the CT image set, deformable registration of CT images, and reoptimization. CONCLUSIONS: Image-guided precision conformal radiotherapy can be used as a tool to treat the tumor yet spare critical structures. Helical tomotherapy has been designed from the ground up as an integrated image-guided intensity-modulated radiotherapy system and allows new verification processes based on megavoltage CT images to be implemented.

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