Patent Publication Number: US-2023138303-A1

Title: Methods of denervating vertebral body using external energy source

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a continuation of U.S. patent application Ser. No. 16/205,050, filed Nov. 29, 2018, which is a continuation of U.S. patent application Ser. No. 14/369,661, filed Jun. 27, 2014, now issued as U.S. Pat. No. 10,390,877, which is a 371 U.S. national phase entry of International Application No. PCT/US2012/071465, filed Dec. 21, 2012, which claims the benefit of U.S. Provisional Application No. 61/582,170 filed Dec. 30, 2011 and U.S. Provisional Application No. 61/582,165 filed Dec. 30, 2011, the entire contents of each of which are hereby expressly incorporated herein by reference. 
    
    
     FIELD 
     Various embodiments of the invention pertain generally to methods and systems for therapeutic treatment of pain, and more particularly to therapeutic treatment of back pain. 
     BACKGROUND 
     Body pain may originate in muscles, organs, bones, or other areas of the body. One example of body pain is back pain, or pain associated with the spine. Back pain is a huge health problem worldwide and is the cause of much human suffering. Back pain is also a major cause for work-related disability benefits and compensation. Treatments for back pain vary widely, ranging from physical therapy, to pharmacological therapy and pain management, to surgical intervention. 
     Use of pharmaceuticals to treat back pain has at least three concerns. First, the patient may become dependent upon the pharmaceuticals. Second, the cost of the pharmaceuticals, usually over several years, may be extremely costly. Third, generally, the pain persists over many years. 
     Surgery also presents several concerns. First, most techniques involve fusing the vertebrae of the spine together and/or removing tissue from between the vertebrae. While surgery usually provides long-term relief, e.g., greater than one-year, surgical techniques require extensive recovery time and additional physical therapy for the patient. 
     While physical therapy does not present all of the concerns of surgery or using pharmaceuticals, patients receive varying degrees of relief from pain. Additionally, physical therapy usually provides only short-term pain relief, e.g., one to two months, thereby extending treatment over several years, and thus increasing the cost of treatment. Moreover, 1 many patients ultimately require surgery. 
     SUMMARY 
     Several embodiments of the invention are directed to a method for treating back pain associated with a vertebral body of a patient, wherein the vertebral body is innervated by a basivertebral nerve having an origin at a medial branch of a sinuvertebral nerve and that courses medially under the posterior longitudinal ligament to enter the vertebral body at a basivertebral foramen of the vertebral body. In some embodiments, the method comprises identifying at least a portion of a basivertebral nerve associated with the vertebral body and isolating the basivertebral nerve at a location external to the vertebral body. In some embodiments, the method comprises modulating (e.g., denervating, temporarily or permanently blocking nerve conduction, altering a conductive property, stimulating, severing, cutting, crimping, heating, cooling, radiating, agitating, or altering the chemical composition of) the basivertebral nerve at the external location to treat pain associated with the vertebral body. 
     Several embodiments of the invention are directed to a method for treating back pain associated with a vertebral body of a patient. In some embodiments, the method comprises percutaneously guiding a delivery device within or near the vertebral body. In some embodiments, the method comprises identifying at least a portion of a basivertebral nerve associated with the vertebral body and isolating the basivertebral nerve at a location external to the vertebral body. In some embodiments, the method comprises delivering a treatment device to the external location using the delivery device and operating the treatment device at the external location. In some embodiments, the operation of the treatment device is configured to modulate the basivertebral nerve at the external location to treat pain associated with the vertebral body. In one embodiment, the delivery device comprises a catheter comprising a first lumen for advancing an imaging device and a second lumen for advancing the treatment device. 
     In some embodiments, the basivertebral nerve comprises a medial branch of a sinuvertebral nerve, wherein the basivertebral nerve emanates at a first end at a junction of the sinuvertebral nerve and wherein the basivertebral nerve courses medially from the junction under the posterior longitudinal ligament. In some embodiments, the basivertebral nerve enters the vertebral body at a second end located at a basivertebral foramen of the vertebral body. Modulation of the basivertebral nerve may be performed at a location on the basivertebral nerve at or near the second end located within the basivertebral foramen. 
     In some embodiments, identifying at least a portion of the basivertebral nerve comprises locating the sinuvertebral nerve and locating the junction of the basivertebral nerve with the sinuvertebral nerve. In one embodiment, modulating the basivertebral nerve comprises modulating the basivertebral nerve at a location on the basivertebral nerve at or near the junction with the sinuvertebral nerve. In one embodiment, the method comprises verifying that the basivertebral nerve courses medially under the posterior longitudinal ligament prior to modulating the basivertebral nerve. In some embodiments, the posterior longitudinal ligament is dilated to allow visualization of the basivertebral foramen prior to modulation of the basivertebral nerve. 
     In several embodiments, isolating the basivertebral nerve comprises following the basivertebral nerve from the junction medially under the posterior longitudinal ligament and dilating a space under the posterior longitudinal ligament to visualize the basivertebral foramen. In one embodiment, the method comprises locating the basivertebral foramen via direct visualization with an imaging device and modulating the basivertebral nerve at a location on the basivertebral nerve at or near the second end located within the basivertebral foramen. 
     In some embodiments, the step of modulating the basivertebral nerve comprises positioning an energy delivery device into the basivertebral foramen and directing a field of energy into the basivertebral foramen to denervate the basivertebral nerve, wherein the directed energy field is focused to be confined in a first direction into the basivertebral foramen. In some embodiments, the step of identifying at least a portion of the basivertebral nerve comprises locating the sinuvertebral nerve via direct visualization with an imaging device and locating the junction of the basivertebral nerve with the sinuvertebral nerve. 
     Several embodiments of the invention are directed to a system for treating back pain associated with a vertebral body of a patient. The system may comprise a delivery assembly configured to be percutaneously delivered to a treatment region adjacent the vertebral body. The delivery assembly may comprise a catheter having one or more lumens and an energy delivery device configured to be advanced within one of the catheter lumens. In some embodiments, the energy delivery device is sized to allow positioning of a distal end of the energy delivery device at a treatment region (such as the origin of the basivertebral nerve with the sinuvertebral nerve, or into the basivertebral foramen). In one embodiment, the energy delivery device comprises an energy delivery element configured to direct a focused field of energy (e.g., for focusing energy into the basivertebral foramen to modulate the basivertebral nerve) such that the directed energy field is focused to be confined in a first 3 direction into the basivertebral foramen. 
     In some embodiments, the energy delivery element is configured to emit therapeutic energy radially outward from the distal end of the energy delivery device while substantially shielding energy delivery toward a proximal end of the energy delivery device. In some embodiments, the delivery assembly comprises an imaging device (e.g., visualization scope or camera) to aid in visualization of the basivertebral foramen and delivery of the energy delivery device into the basivertebral foramen. In one embodiment, the delivery assembly comprises an aspirating device to be delivered under the posterior longitudinal ligament via the one ore more lumens of the catheter. The aspiration device may be configured to dilate a space under the posterior longitudinal ligament to aid in visualization of the basivertebral foramen. 
     Several embodiments of the invention are directed to a method for denervating a basivertebral nerve to treat back pain using an externally positioned energy source (e.g., radiation, ultrasound, microwave source). The energy source may comprise a plurality of sources. The plurality of sources may be configured to deliver different energy modalities and/or deliver energy at different times. In one embodiment, the method includes acquiring imaging data of the vertebra. In one embodiment, the method comprises determining a target treatment site within or near the vertebra based on the acquired imaging data that corresponds to a location of a basivertebral nerve associated with pain in the vertebral body. In one embodiment, the step of determining a target treatment site is performed visually without acquiring imaging data. In one embodiment, the method comprises positioning a focal point of an external energy source to substantially coincide with the target treatment site. The target treatment site may be within or outside the vertebral body. The target treatment site may correspond to a location of a basivertebral nerve associated with pain in the vertebral body. In several embodiments, the target treatment site is a location within a basivertebral foramen of the vertebral body. 
     In one embodiment, the external energy source is positioned at a location external to the body of a patient. In one embodiment, the method comprises delivering a treatment dose of therapeutic energy at the target treatment site, wherein the treatment dose is configured to modulate (e.g., denervate, temporarily or permanently block or eliminate nerve conduction, alter a conductive property, stimulate, heat, cool, radiate, agitate, disrupt, ablate, or alter the chemical composition of) the basivertebral nerve. 
     In one embodiment, the method comprises acquiring patient feedback prior to delivering the treatment dose (e.g., using one or more sensors or monitors or through  4  conversation with the patient). In one embodiment, acquiring patient feedback comprises delivering an identification dose that is a lesser dose than the treatment dose to the target treatment site and eliciting feedback from the patient with respect to a change in the sensation of pain. The identification dose may be prescribed such that the identification dose temporarily alters the sensation of pain experienced by the patient. In one embodiment, the method comprises modifying the target treatment site or location according to the acquired feedback. 
     Treatment may be delivered to the target treatment site to modulate at least a portion of the basivertebral nerve (e.g., terminus or junction or a portion of the basivertebral nerve between the terminus or junction and the posterior wall). In one embodiment, a portion of the basivertebral nerve is modulated by delivering focused energy (e.g., radiation, acoustic or ultrasonic energy) to an isolated region of the basivertebral nerve. In one embodiment, the focused energy is high-intensity focused ultrasonic energy. In another embodiment, a portion of the basivertebral nerve is modulated by delivering an agent to the treatment region to isolate treatment to that region. In accordance with several embodiments of the invention, the treatment is advantageously focused on a location of the basivertebral nerve that is upstream of one or more branches of the basivertebral nerve. 
     In some embodiments, delivering the treatment dose comprises delivering a first incremental dose that is a fraction of the treatment dose and then acquiring imaging data of the patient. The method may comprise measuring the distance between the focal point of the energy source and the target treatment site and then moving the external energy source such that the focal point of the external energy source coincides with the target treatment site if the measured distance is not within a predetermined threshold. In some embodiments, delivering the treatment does comprises delivering a second incremental dose if the measured distance is within the predetermined threshold. 
     Nerves within bones other than the vertebrae or spine may be targeted by the external energy source, for example, non-spinal joints or in non-orthopedic applications (e.g., cardiac, pulmonary, renal, or treatment of other organs and/or their surrounding nerves). The external energy source may comprise at least one radiation source or at least one acoustic energy source. In one embodiment, the at least one acoustic energy source comprises one or more transducers configured to deliver focused ultrasonic energy (e.g., high-intensity focused ultrasonic energy or low-intensity focused ultrasonic energy). In one embodiment, the external energy source comprises at least one microwave source. 
     In some embodiments, the step of determining a target treatment site 5 comprises acquiring a vertebral reference point corresponding to a radiographically identifiable anatomical feature of the vertebra and generating coordinates for the target treatment site as a function of a calculated distance from the vertebral reference point. In one embodiment, the calculated distance corresponds to a predicted basivertebral nerve location that is obtained from analysis of the acquired imaging data. 
     In some embodiments, the step of acquiring imaging data comprises restraining at least a portion of the patient to an external support. In one embodiment, the external support comprises a radiographically identifiable marker. Acquiring imaging data may comprise imaging the patient and locating the radiographically identifiable marker within the acquired image. The method may comprise assigning an external reference point corresponding to the location of the radiographically identifiable marker. In one embodiment, the external reference point is as a base point for positioning the focal point of the external energy source at the target treatment site. In one embodiment, the method comprises acquiring a vertebral reference point corresponding to a radiographically identifiable anatomical feature of the vertebra and generating coordinates for the target treatment site as a function of a calculated distance from the vertebral reference point. In some embodiments, the step of determining a target treatment site is performed by direct visualization without calculations based on acquired imaging data. 
     Several embodiments of the invention are directed to a system for treating back pain associated with the spine (e.g., one or more vertebrae) of a patient. In several embodiments, the system provides non-invasive treatment of the back pain by modulating spinal nerves (e.g., intraosseous or basivertebral nerves) from outside the body. In some embodiments, the system comprises an external energy (e.g., radiation) source configured to be positioned at a location external to the body of the patient. In one embodiment, the system comprises a linear drive configured to drive translation of the external energy source with respect to the patient in one or more axes. In one embodiment, the system comprises a computer coupled to the external energy source and to the linear drive. In one embodiment, the system comprises programming instructions executable on the computer. In several embodiments, the programming instructions comprise one or more modules for performing one or more of the following: determining a target treatment site within or near the spine (e.g., vertebral body) based on acquired imaging data or based on direct visualization; controlling the linear drive to position a focal point of the external energy source to substantially coincide with a target treatment site that corresponds to a location of a basivertebral nerve associated with pain in the spine (e.g., vertebral body); and controlling the  6  external energy source to deliver a treatment dose of therapeutic energy at the target treatment site. In several embodiments, the treatment dose is configured to modulate (e.g., denervate) the basivertebral nerve. The therapeutic system may include a treatment device and an imaging device. In one embodiment, the treatment device and the imaging device are combined into a single unitary device. The focal point may be adjusted depending on imaging obtained by the imaging device or other feedback mechanisms. 
     In some embodiments, the system comprises an imaging source coupled to the computer for acquiring imaging data of the spine (e.g., vertebrae or vertebral bodies). In one embodiment, the system comprises a support configured to restrain at least a portion of the patient to an external support. The support may comprise a radiographically identifiable marker. In one embodiment, the executable program instructions are configured to control the imaging source for imaging the patient, locate the radiographically identifiable marker within the acquired image; and assign an external reference point corresponding to the location of the radiographically identifiable marker. The external reference point may be used as a base point for positioning the focal point of the external energy source at the target treatment site. 
     In some embodiments, the system comprises a radial drive coupled to the external energy source. The radial drive may be configured to rotate the external energy source about the target treatment site during delivery of the treatment dose. The external energy source may comprise one or more radiation-emitting and/or acoustic energy sources having a common focal point or different focal points. 
     Several embodiments of the invention are directed to a radiotherapy method for treating back pain associated with a vertebral body of a vertebra of a patient. In one embodiment, the method comprises acquiring imaging data of the vertebra and determining a target treatment site within the vertebra based on the acquired imaging data. In one embodiment, the target treatment site corresponds to a location of a basivertebral nerve associated with pain in the vertebral body. The method may further comprise positioning a focal point of an external radiation source to substantially coincide with the target treatment site and delivering a treatment dose of therapeutic energy at the target treatment site to modulate the basivertebral nerve. 
     Several embodiments of the invention are directed to a radiotherapy system for treating back pain associated with a vertebral body of a patient. In some embodiments, the system comprises an external radiation source configured to be positioned at a location external to the body of the patient. In one embodiment, the system comprises a 7 linear drive coupled to the radiation source, the linear drive configured to drive translation of the radiation source in one or more axes. In some embodiments, the system comprises a computer coupled to the radiation source and to the linear drive. The computer may comprise programming instructions executable on the computer for determining a target treatment site within or near the vertebra based on acquired imaging data, wherein the target treatment site corresponds to a location of a basivertebral nerve associated with pain in the vertebral body. In one embodiment, the programming instructions are further configured to control the linear drive to position a focal point of the external energy source to substantially coincide with the target treatment site and/or to control the external radiation source to deliver a treatment dose of therapeutic energy at the target treatment site. In some embodiments, the treatment dose is configured to modulate the basivertebral nerve at the location. 
     Further aspects of embodiments of the invention will be discussed in the following portions of the specification. With respect to the drawings, elements from one figure may be combined with elements from the other figures. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       Several embodiments of the invention will be more fully understood by reference to the following drawings which are for illustrative purposes only: 
         FIG.  1    illustrates a left posterior view of the lumbar spine showing branches of associated nerves. 
         FIG.  2    is a posterior view of the spine, with pedicles transected, dural sac removed to show the path and branches of the left sinuvertebral nerve. 
         FIG.  3    is a posterior view of the spine, with pedicles transected and dural sac removed, and posterior longitudinal ligament cut out to show the path and branches of the left sinuvertebral nerve. 
         FIG.  4    shows a posterior view of the spine showing the basivertebral nerve emanating from a bifurcated branch of the sinuvertebral nerve. 
         FIG.  5    shows a posterior view of another spine sample showing the basivertebral nerve emanating from a bifurcated branch of the sinuvertebral nerve. 
         FIG.  6    illustrates a cross-sectional view of a vertebral body shown in  FIG.  1   . 
         FIG.  7    illustrates a schematic diagram of an embodiment of a method for treatment of pain via denervation of the basivertebral nerve at a location external to the vertebral body. 
         FIG.  8    illustrates a schematic diagram of an embodiment of a method for identifying the basivertebral nerve. 
         FIG.  9    illustrates a schematic diagram of an embodiment of a method for isolating the basivertebral nerve. 
         FIG.  10    shows an embodiment of a delivery and treatment system for minimally-invasively treating the basivertebral nerve at a location external to the vertebral body. 
         FIG.  11    shows a distal-end view of an embodiment of a delivery assembly. 
         FIG.  12    illustrates cut-out side view of a lumber vertebra. 
         FIG.  13    illustrates a cut-out top view of a vertebral body showing placement of an embodiment of a treatment delivery assembly within a first of two basivertebral foramen. 
         FIG.  14    illustrates a cut-out top view of a vertebral body showing placement of an embodiment of a treatment delivery assembly within a vertebra having one basivertebral foramen. 
         FIG.  15    is a picture of a cadaver showing numerous small neural elements converged on the foraminal ostia. 
         FIG.  16    is a picture of a cadaver showing larger, more singular nerves observed entering from the general region of the nerve root. 
         FIG.  17    is a picture of a cadaver showing largest medial branch of the sinuvertebral nerve. 
         FIG.  18    is another picture of a cadaver of  FIG.  17   . 
         FIG.  19    is a block diagram of an embodiment of a radiotherapy apparatus for treating back pain. 
         FIG.  20    is a schematic diagram of an embodiment of the radiotherapy apparatus of  FIG.  19   . 
         FIG.  21    is a sectional view of an embodiment of the radiotherapy gantry of  FIG.  20   . 
         FIG.  22    is a side view of a lumbar vertebra showing innervation of the vertebral body. 
         FIG.  23    is a top view of the lumber vertebra of  FIG.  22   . 
         FIG.  24    is flow diagram of an embodiment of a radiotherapy method for treating back pain. 
         FIG.  25    is an embodiment of a flow diagram of the treatment delivery method of  FIG.  24   . 
     
    
    
     DETAILED DESCRIPTION 
     In accordance with several embodiments, back pain may be associated with one or more nerves in the spine. For example, one or more intraosseous or basivertebral nerves within one or more vertebrae of the spine may be the source of the back pain. In some embodiments, the nerves are treated (e.g., modulated) at nerve portions that are isolated outside of the bony tissue of the vertebral body (e.g., external to the vertebral body). In some embodiments, the nerves are treated from a location external to the skin (e.g., extracorporeal, non-invasive) treatment. 
     Identification, Isolation, and Modulation of Basivertebral Nerve 
       FIG.  1    illustrates a left posterior view of the lumbar spine  10  showing branches of associated nerves. Spine  10  comprises intervertebral discs  14  disposed between adjacent vertebrae  12 . Lumbar dorsal rami  18  branch at nearly right angles from a corresponding ventral ramus  16  at each vertebra  12 . The dorsal rami  18  divide into two or three branches: medial branch  20 , lateral branch  22 , and variable intermediate branch  21 . 
     Referring to  FIGS.  2  and  3   , the sinuvertebral nerves  28  (left and right) are recurrent branches of the ventral rami  16  that re-enter (e.g., retrograde) the intervertebral foramina  25  to be distributed within the vertebral canal  46 .  FIG.  2    is a posterior view of the spine  10  with pedicles  26  transected, dural sac removed to show the path and branches of the left sinuvertebral nerve  28  (posterior longitudinal ligament  32  is intact).  FIG.  3    is a posterior view of the spine  10  with pedicles  26  transected and dural sac removed, and posterior longitudinal ligament  32  cut out to show the path and branches of the left sinuvertebral nerve  28  and floor of the vertebral canal  46 . In  FIG.  3   , the ventral ramus  16  and dorsal root ganglion  18  are retracted to show the originals of the origin of the sinuvertebral nerve  28 . 
     As shown in  FIG.  3   , the sinuvertebral nerves  28  are mixed polysegmental nerves and nerve plexuses, each being formed by a somatic root  36  from a ventral ramus  16  and an autonomic root  38  from the grey ramus communicans  34 . The lumbar sinuvertebral nerves  28  run across the back of the vertebral body  40 , just below the upper pedicle  26 . Within the vertebral canal  46 , the sinuvertebral nerve  28  forms a major ascending branch  35  travelling nostrally parallel to the posterior longitudinal ligament  32 , a lesser descending branch  33 , and a larger medial branch  30  that crosses under the posterior longitudinal ligament  32 . 
     In accordance with several embodiments, the medial branch  30  comprises the basivertebral nerve that innervates the vertebral body  40 , and is in large part responsible for back pain experienced by a subject (e.g., human or animal patient). 
       FIG.  3    illustrates a basivertebral nerve  30  that emanates from a trifurcated junction  31  of the sinuvertebral nerve  28 , comprising ascending branch  35 , descending branch  33  and medial basivertebral nerve branch  30 . As seen in  FIG.  3   , the basivertebral nerve extends from trifurcated junction  31  below the posterior longitudinal ligament  32  and into one of the basivertebral foramina  42 . The basivertebral nerve  30  shown in  FIG.  3    is the left basivertebral nerve that enters the left-most basivertebral foramen  42 . Correspondingly, the right basivertebral nerve (not shown) follows a similar path from under the opposite pedicle  26  and into the right basivertebral foramen  42 . 
       FIGS.  4  and  5    are similar posterior views of the spine  10  showing the basivertebral nerve  30  emanating from a bifurcated junction  37  of the sinuvertebral nerve  28 . In each of these cases, the lesser descending branch  33  is formed from a first junction with the ascending branch  35  of the sinuvertebral nerve  28 . The basivertebral nerve  30  then emanates from the ascending branch  35  at the bifurcated junction  37 , and runs medially under the posterior longitudinal ligament  32  and into the basivertebral foramen  42 .  FIG.  5    shows an example where the bifurcated junction (e.g., basivertebral nerve junction)  37  is closer to the origination of the sinuvertebral nerve  28  with somatic root  36  and anatomic root  38 . 
     The basivertebral nerve  30  comprises the largest medial branch emanating from the sinuvertebral nerve  28 , which runs medially under the posterior longitudinal ligament  32 . The basivertebral nerve  30  travels into the basivertebral foramen  42  to innervate the vertebral body. 
       FIG.  6    illustrates a cross-sectional view of the vertebral body  12  shown in  FIG.  1   , with associated anatomy. As shown in  FIG.  6   , the left and right basivertebral nerves  30  emanate from the sinuvertebral nerve  28  and travel medially under the posterior longitudinal ligament  32  and into the vertebral foramina  46 . Each corresponding basivertebral nerve  30  then enters corresponding left and right basivertebral foramen  42 , where they generally bundle with basivertebral blood vessels  43  and travel to the end of the conical-shaped basivertebral foramen  42  to then enter the bony mass of the vertebral body  40 . In some cases, there may only be one basivertebral foramen (shown in  FIG.  13   ), and both left and right basivertebral nerves may travel toward the distal end of the same basivertebral foramen. 
       FIG.  7    illustrates a schematic diagram of an embodiment of a method  100  for treatment of pain via modulation of the basivertebral nerve  30  within a patient. In accordance with several embodiments, access to the basivertebral nerve  30  for subsequent intraosseous nerve modulation (e.g., ablation, denervation, stimulation) may be achieved in at least two ways. In a first “minimally invasive” approach, the patient&#39;s skin may be penetrated with a surgical instrument, which is then used to access the desired basivertebral nerves, e.g., percutaneously. 
     In a second “open” approach, the intraosseous nerves (e.g., basivertebral nerves) may be modulated during an open surgery or surgical repair of the spine  10 , wherein the patient&#39;s spine, or a portion thereof, is fully exposed for the primary surgery (e.g., vertebral fracture repair, spinal fixation, tumor removal, etc.). The basivertebral nerves  30  may be permanently or temporarily denervated (e.g., ablated, cut, crimped) as a prophylactic measure against subsequent post-surgical back pain. In some embodiments, intraosseous nerve modulation (e.g., ablation, denervation, stimulation) may also occur prior to the primary spinal surgery. 
     Regardless of whether the basivertebral nerve modulation is performed percutaneously or as a secondary procedure during a conventional spinal surgical repair, the following discussion is directed to various embodiments of surgical methods for accessing basivertebral nerves. While the following description is limited to three different approaches for accessing the basivertebral nerves, alternative approaches may be taken by the surgeon depending upon the clinical setting without varying from the spirit and/or scope of the disclosure. 
     Referring back to  FIG.  7   , in accordance with several embodiments, the first step  102  in method  100  is to identify at least a portion of the left or right basivertebral nerve  30  for the particular vertebral body of interest (e.g., the L3, L4, L5, S1, or S2 vertebra). Next, at step  104 , a portion of the basivertebral nerve  30  is isolated at a location outside the vertebral body. In some implementations, the isolation is achieved by locating the origin of the basivertebral nerve  30  with the sinuvertebral nerve  28  at junctions  31  or  37  (see  FIGS.  3 - 5   ). In some implementations, the isolation is achieved by locating the entry of the basivertebral nerve  30  into the vertebral body  40  (e.g. at basivertebral foramen  42  shown in  FIG.  7   ). Identification and/or isolation at steps  102  and  104  may be performed via direct visualization with a catheter-based delivery system  200 , as shown in  FIGS.  10  and  11   , or with an external imaging system (e.g., ultrasound, optical coherence tomography, MR imaging, CT imaging, Doppler, X-ray). 
     Referring to  FIG.  8   , in accordance with several embodiments, step  104  (isolating the basivertebral nerve  30  at junctions  31  or  37 ) is first performed by locating the sinuvertebral nerve  28  at step  110 . In some embodiments, locating the sinuvertebral nerve  28  is performed percutaneously through intervening facie and tissues. Next, at step  112 , the sinuvertebral nerve  28  is followed away from its origination ascending upward until the largest medial branch  30  is located at trifurcated junction  31  (trifurcated branch shown in  FIG.  3   ) or bifurcated junction  37  (bifurcated branch shown in  FIGS.  4  or  5   ). The determination may then be verified at step  114  by verifying that the branch of the basivertebral nerve  30  runs under the posterior longitudinal ligament  32 . 
     Referring to  FIG.  9   , in accordance with several embodiments, locating the entry of the basivertebral nerve  30  into the vertebral body  40  via step  104  may be performed by first following the medial branch  30  under the posterior longitudinal ligament  32  at step  120 . In some embodiments, the space under the posterior longitudinal ligament  32  may then be dilated at step  122  to visualize the space underneath the posterior longitudinal ligament  32 . The medial branch  30  may then be followed into the basivertebral foramen  42  at step  124 . In some embodiments, to locate the entry of the basivertebral nerve  30  into the vertebral body  40 , an alternative approach may be to dilate the posterior longitudinal ligament  32  and identify and/or visualize the basivertebral foramen  42  without identifying or following the medial branch of the sinuvertebral nerve  28 . By locating basivertebral foramen  42 , the basivertebral nerve  30  is also located, as the basivertebral nerve enters the vertebral body  40  via the basivertebral foramen  42 . 
     Referring back to  FIG.  7   , in accordance with several embodiments, once the basivertebral nerve  30  is located and isolated for treatment, the desired treatment location of the basivertebral nerve  30  is denervated at step  106 . For purposes of this disclosure, the terms “modulate” or “neuromodulate” as used herein, shall be given their ordinary meaning, and shall include modifying the conductive properties of the nerve, such that the transmission of signals from the nerve endings within the vertebral body are stimulated, altered, blocked, or eliminated altogether, to provide a therapeutic effect within or related to the vertebral body. Modulation shall also include ablation, denervation, disruption, inhibition, therapeutic stimulation, diagnostic stimulation, necrosis, desensitization, or other effect on tissue. Neuromodulation shall refer to modulation of a nerve (structurally and/or functionally) and/or neurotransmission. Modulation is not limited to nerves and may include effects on other tissue. Modulation may comprise a partial or total and/or partial or temporary loss or alteration of conduction of the nerve across the location for treatment of the nerve. In several embodiments, modulating (e.g., denervating) the nerve may be achieved by cutting, crimping, heating, cooling, radiating, agitating, or altering the chemical composition of the nerve at the treatment location. 
     The goal of the treatment or modulation (e.g., denervation) may be ablation or necrosis of the target nerve or tissue, or some lesser degree of treatment to denervate the basivertebral nerve. For example, the treatment energy, frequency and/or other treatment parameters may be just sufficient to stimulate the nerve to block the nerve from transmitting signals (e.g., signals indicative of pain). 
     In one embodiment, the treatment system  200  (shown in  FIGS.  10  and  11    and described in further detail below) may comprise a number of different treatment modalities for therapeutic treatment of the target region. For example, in one embodiment, the treatment devices or probes in system  200  operate in a manner that produces heat or thermal energy (such as described in U.S. Pat. No. 6,699,242, herein incorporated by reference in its entirety) that modulates (e.g., ablates) the tissue of the target region (e.g., a basivertebral nerve) at the target region (e.g., a basivertebral nerve location). In some embodiments, the treatment devices or probes in system  200  operate in a manner that produces acoustic energy. The treatment devices or probes may include one or more energy sources (e.g., RF energy sources, ultrasonic transducers or elements, microwave energy sources, light energy sources, plasma ion sources). In some embodiments, energy sources of different energy modalities may be used in combination. For example, one energy source may emit ultrasound energy while another energy source may emit microwave or electrical energy. The energy output may be dynamically controlled by changing the power intensity, the frequency, the angle of dispersion, the focus, or other dynamically controllable parameters. In some embodiments, the treatment devices or probes in system  200  comprise surgical cutting devices or fluid delivery devices. In one embodiment, the treatment device s or probes comprise a bipolar RF probe with a pair of electrodes. In some embodiments, the fluid delivery device comprises a catheter, tube, sleeve, needle, cannula, wicking device, or other conduit configured to deliver fluid. The fluid may comprise neurolytic agents, chemotherapy agents, radioactive substances, medications, drugs, pharmaceuticals, alcohols, acids, solvents, cooling agents, nerve blocking agents, and/or other chemical agents. 
     In one embodiment, the treatment device is configured to deliver therapeutic treatment that is targeted to block nerve conduction without ablating the nerve (e.g., treatment is delivered to the nerve via thermal therapy, chemical agent, or the like) that results in denervation of the basivertebral nerve without necrosis of tissue. This may be achieved via delivery of a lesser amount of energy or agent to the tissue site (either in the form of less exposure time, concentration, intensity, etc.) than is required for ablation, but an amount sufficient to achieve some amount of temporary or permanent denervation. In some embodiments, the treatment device is configured to stimulate nerves. 
     In one embodiment, dosing of the treatment therapy may be tailored to the desired goal for modulation, the region or type of tissue to be treated, and the modality being used, among other factors. 
     In one embodiment, when heating is the applied modality, a minimum dose threshold of 30 CEMs (Cumulative Equivalent Minutes), with temperatures between 40° C. and 100° C. (e.g., between about 40° C. and about 60° C., between about 40° C. and about 80° C., between about 50° C. and about 90° C., between about 60° and about 100° C., between about 50° C. and about 80° C., or overlapping ranges thereof) is applied for some tissues. In some embodiments, cooling is administered to the target tissue (using either the treatment device or a separate device. 
     In some embodiments, a thermal dose of 300 CEMs may be used to ablate tissues, and sometimes the dose may reach 1000 CEMs or more. The delivered dose may be a function of several different variables: e.g., tissue type, thermal conduction of the surrounding tissues, treatment region, treatment type, and other uncontrolled variables. In various embodiments, the thermal dose may be between about 30 and about 1000 CEMs, between about 100 and about 500 CEMs, between about 50 and about 300 CEMs, between about 200 and about 400 CEMs, between about 300 and about 800 CEMs, between about 400 and about 900 CEMs, between about 500 and about 1500 CEMs, or overlapping ranges thereof. 
     In some embodiments, such as when RF energy is used, the impedance of the target tissue may also have an effect and be factored in the desired dosing treatment plan. If ultrasound energy is used, the propagation of the energy through the tissues is a major factor, (e.g., ultrasound generally propagates better through soft tissues than hard tissues, such as bone). Propagation of the energy (e.g., via ultrasound or RF) may be also be enhanced or modified by other substances added to the local tissues. The ultrasound energy may be used for cavitation or non-cavitation. 
     In one embodiment, the material used to enhance the conduction of the energy may be a biological material such as blood. In some embodiments, the biological material may serve to enhance the energy delivery while simultaneously acting as an insulator for another area of the body. For example, delivery of blood may enhance the propagation of thermal energy at some temperatures, but may act as in insulator if exposed to higher temperatures, thus effectively blocking the transmission of potently damaging thermal energy to other neighboring nerves or anatomy once a threshold temperature is exceeded.). In embodiments where RF energy is used for heating the nerve or other target tissue, the frequency may be any integer between about 100 kHz and 1 MHz, between 400 kHz and 600 kHz, between 300 kHz and 500 kHz, between 350 kHz and 600 kHz, between 450 kHz and 600 kHz, between 300 kHz and 450 kHz, between 350 kHz and 500 kHz, between 400 kHz and 600 kHz, between 450 kHz and 550 kHz, between 460 kHz and 500 kHz overlapping ranges thereof, or any frequency within the recited ranges. 
     For stimulation of the nerve using RF energy, in accordance with several embodiments, the frequency may be applied at a substantially lower level, e.g., in the range of approximately 1 Hz to 200 kHz, and may be used in a pulsed or continuous mode. In one embodiment, the total CEMs in the stimulation mode are maintained below 30 to limit tissue damage. Pulsed energy may be used to stimulate the nerve in one mode and then the frequency, pulse width or intensity may be modulated (e.g., increased) to achieve ablative/destructive doses of energy. In one embodiment, stimulation of the nerve is performed to block the travel of signals indicative of pain. Stimulation may comprise mechanical, electrical, or electromechanical stimulation. 
     Each vertebra generally comprises a left and right basivertebral nerve  30  that leads into the vertebral body  40 . Accordingly, once a first side (e.g. left side) is treated, the procedure may then be repeated for the corresponding opposite side (e.g. right side). In some embodiments, a “side” is defined by a center line extending from the center of the posterior outer cortical wall to the center of the anterior cortical wall. In other embodiments, “side” can be defined by any line extending through the center of the vertebral body. 
     Patient feedback may be acquired at particular stages within the procedure. For example, in one embodiment, the target region of the basivertebral nerve  30  may be heated at a lower, non-destructive or “stimulating” level to generate a desired temporary therapeutic response from the patient. Patient feedback may then be obtained to verify that the location is correct before a destructive or permanent dose is delivered. 
       FIG.  10    shows one embodiment of a delivery and treatment system  200  for minimally-invasively treating the basivertebral nerve  30  at a location external to the vertebral body. System  200  comprises a delivery assembly  202 , such as the multi-lumen catheter  202 , that is configured to be introduced into the body subcutaneously and delivered to the basivertebral nerve  30  at one its junctions  31 ,  37  with sinuvertebral nerve  28 , and/or to the basivertebral foramen  42  under the posterior longitudinal ligament  32 . 
     In some embodiments, the treatment system  200  comprises a treatment device  204  for achieving the desired denervation at the treatment location at the basivertebral nerve  30 . The treatment device  204  may be configured to deliver any number of treatment modalities (singly or in combination) at the treatment site for therapeutic denervation of the basivertebral nerve  30  or other nerves within bone. For example, treatment may be affected by monopolar, bipolar or tripolar RF, ultrasound, acoustic, radiation, steam, microwave, laser, light, or other heating means. Additionally, in some embodiments, the treatment device  204  may comprise a fluid delivery catheter that deposits an agent (e.g., bone cement, chemoablative fluid, radioactive substance, or other therapeutic agent) to the treatment location at the basivertebral nerve  30 . In one embodiment, cryogenic cooling may be delivered for localized treatment of the basivertebral nerve  30 . In one embodiment, treatment may be affected by any mechanical destruction and or removal means capable of severing or denervating the basivertebral nerve  30 . For example, a cutting blade, bur or mechanically actuated cutter may be used to affect denervation of the basivertebral nerve  30 . 
     In accordance with several embodiments, and in addition to or separate from treating the basivertebral nerve, a sensor (not shown) may be delivered to the region to preoperatively or postoperatively measure nerve conduction or heating at the treatment region. In this configuration, the sensor may be delivered on a distal tip of a flexible probe that may or may not have treatment elements (e.g., electrodes, ultrasound transducers, microwave elements) as well. 
     In one embodiment, system  200  comprises a camera  208  or other imaging device sized to be received within delivery assembly  202 . The camera  208  can be configured to provide visualization of the nerves and surrounding anatomy for navigating to the proper location and identification of the basivertebral nerve  30  and surrounding anatomy. The imaging device can comprise one or more optical fibers for lighting and/or one or more optical fibers for imaging. 
     In one embodiment, system  200  further comprises an aspiration device  206  sized to be received within delivery assembly  202  for delivering fluid to the region (e.g., under the posterior longitudinal ligament  32  to dilate a space under the posterior longitudinal ligament  32  for visualization of the basivertebral nerve  30 , basivertebral foramen  42 , or other anatomy). Aspiration of the surrounding anatomy may be used for navigating to the proper location and identification of the basivertebral nerve  30  and surrounding anatomy (e.g. sinuvertebral nerve,  28  and/or basivertebral foramen  42 ). 
     In one embodiment, system  200  may comprise a secondary visualization and/or imaging means  210 , such as radiographic (x-ray) imaging, to be used in combination with, or in alternative to, direct imaging. For example, the basivertebral foramen  42  may be located via radiographic imaging for direct treatment of the basivertebral nerve  30  within the basivertebral foramen. 
       FIG.  11    shows a distal-end view of one embodiment of a delivery assembly  202 . Delivery assembly  202  may comprise a multi-lumen catheter with a plurality of lumens  220 ,  222 , and  224  for minimally-invasively delivering diagnostic and treatment instruments to the treatment location. 
     In one embodiment, catheter  202  comprises a first lumen  220  for delivery of a camera  208  or other imaging device. In some embodiments, catheter  202  comprises a second delivery lumen  222  for delivery of a treatment device  204 , which may comprise a treatment element  212 . Treatment element  212  may comprise an energy/therapy delivery applicator (e.g., RF element, agent delivery lumen, cutting blade, or the like) for treatment of the basivertebral nerve  30  at the treatment location. In one embodiment, catheter  202  comprises a third lumen  224  for delivery of an aspiration device  206  simultaneously with either the imaging device  208  or treatment device  204 . 
     As explained above, the treatment location may comprise the location of the basivertebral nerve  30  at the entry point within the vertebral body  40  within the basivertebral foramen  42 .  FIGS.  12 - 14    show the basivertebral foramen  42  and one embodiment of the treatment assembly  202  delivered at the treatment location within the basivertebral foramen  42 . 
       FIG.  12    illustrates a cut-out side view of a lumber vertebra  12 . As shown m the cutout m vertebral body  40 , the basivertebral foramen  42  is a conical opening emanating from the spinal canal  46  and generally positioned along the midline of the vertebral body  40 . Previous systematic histological analysis of the vertebral body  40  has established the predominant entry point for vertebral intraosseous nerves as the basivertebral foramen  42 , and the major source of innervation of the vertebral body  40  as the basivertebral nerve  30 . The large basivertebral foramina  42  universally penetrate the posterior cortex of the vertebral body  40  at a midline of the vertebral body. The basivertebral nerves (which arise as a branch of the sinuvertebral nerve, which in turn anastomoses with the sympathetic chain) enter the vertebral body  40  through these foramina  42 , arborize and innervate the vertebral body  40  down to and including the endplates. Nociceptive function of these basivertebral nerves has been confirmed by staining. 
       FIG.  13    illustrates a cutout top view of a vertebral body showing placement of one embodiment of a treatment delivery assembly  202  within a first of two basivertebral foramen  42 . In one embodiment, the treatment device  204  is delivered into the basivertebral foramen  42  and then actuated to modulate (e.g., denervate) the basivertebral nerve  30  (this location may comprise multiple branches of the basivertebral nerve  30 ) within the cavity of the basivertebral foramen  42 .  FIG.  13    is shown with one embodiment of an energy delivery device (e.g. ultrasound or RF applicator) delivering a field of energy E into the basivertebral foramen  42  to denervate the basivertebral nerve  30 . Other modalities (e.g., cutting blade, agent delivery, etc.) may also be delivered into the cavity  42  with appropriate non-energy delivery devices. In one embodiment, energy is delivered radially outward and/or forward into the cavity  42  so as to form a conduction block of the basivertebral nerve  30  toward at least one location within the basivertebral foramen  42 . The field of energy may be delivered omnidirectionally or in a controlled direction. Device  204  may comprise shielding or directed energy delivery so as not to direct energy backward into the spinal canal  46 , and only direct energy into the basivertebral foramen  42 , where the energy is contained within the bony walls of the basivertebral foramen  42 . 
     In one embodiment, once the first basivertebral nerve  30  is treated within the first basivertebral foramen  42 , the treatment device  204  may then be disposed in the other basivertebral foramen  42  to treat the basivertebral nerve  30  on the other side. This may be achieved by advancing treatment assembly  202  further within the canal  46 , or by accessing the other basivertebral foramen  42  from the opposite side of the vertebra  12 . 
     In one embodiment, the basivertebral foramen  42  is accessed through a transpedicular approach, where a channel (shown as dashed lines in  FIG.  13   ) is bored into pedicle  26 . The channel may generally comprise a curved channel based on the location and size of the basivertebral foramen  42 , and bored with instruments and methods as detailed in U.S. Patent Pub. No. 2010/0324506, filed on Aug. 26, 2010, and U.S. patent application Ser. No. 13/612,541, filed on Sep. 12, 2012, each of which is incorporated by reference herein in its entirety. 
     As seen in  FIG.  14   , the vertebra  12  may only comprise one basivertebral foramen  42 . In this case, the treatment delivery assembly  202  and treatment device  204  are delivered into the singular basivertebral foramen  42 , and may deliver energy field E to treat both left and right basivertebral nerves  30  simultaneously. 
     Cadaver Study of the Proximal Basivertebral Neuroanatomy 
     The following study was performed on the neuroanatomy of the proximal basivertebral system, with the specific objective of identifying neural components entering the basivertebral foramina, and tracing the primary basivertebral nerve to a point of origin. A series of three cadaver studies were conducted to identify the origination of the basivertebral nerve and path into the vertebral body. The three cadaver studies are non-limiting examples of embodiments of identification of basivertebral nerve origin. 
     Cadaver Dissection I (Cadaver A) 
     With the cadaver in the prone position, a midline incision was made over the lumbar spine from L2 to S1 and extended laterally 10 cm at each end into an ‘H’. The paraspinal muscles and other soft tissues were elevated and dissected clear of the posterior spine with sharp dissection, and the lamina exposed. The dorsal spine and lamina were totally excised utilizing an oscillating saw, exposing the spinal canal and cord (within the dura) and the dorsal ganglia. 
     The cord was gently retracted with dural retractors, ligatures placed for traction, and the Posterior Lateral Ligament isolated and gently elevated clear of the posterior spinal canal with blunt dissection technique. 
     The adherent elements of soft tissue were gently cleared by blunt dissection using alternating saline saturated and dry gauze sponges, exposing elements of the neural network and the basivertebral foramina. Further local dissection at each foramen was conducted to provide visibility for specific appreciation of the various elements entering the foramina. 
     Referring to  FIG.  15   , it was observed that numerous small neural elements converged on the foraminal ostia, which then generally followed the vascular elements into the vertebral body, forming a classic neurovascular bundle. As seen in  FIG.  16   , larger, more singular nerves were observed entering from the general region of the nerve root. Due to the mechanical disruption of soft tissue in this area from the laminectomy, the exposure utilized rendered tracing these nerves entering the canal to their point of origin (from inside the canal tracing outwards) unfeasible in this cadaver. It was determined that a subsequent dissection utilizing an alternate approach would be conducted focusing on the post-ganglionic anatomy, tracing any nerves entering the canal from that region (from outside the canal tracing inwards). 
     Cadaver Dissection II (Cadaver B) 
     With the cadaver in the prone position, a midline incision was created overlying the Lumbar spine approximately 20 cm in length. Sharp dissection was used to expose the posterior aspect of the lumbar spinous processes. With these landmarks well exposed, the incision was extended laterally approximately 5 cm in each direction at both ends of the original incision to create a very wide exposure (in the shape of an “H”). Following this, the lamina and facet joints of L1, L2, L3, and L4, were widely exposed. Rongeurs and osteotomes were then used to remove the facet joints, lamina, and ligamentum flavum creating a wide exposure of the dura, the Dorsal Root Ganglion, and exiting nerve roots. Pedicles were divided on the coronal plane. 
     Beginning on the left side, the nerve roots were divided as they exited the central dural sac. The central dura thus drained of CSF, collapsed and was gently retracted medially out of the field. The root itself was then gently retracted laterally. With careful elevation of the nerve root, the sinuvertebral nerve was easily identified at each of the levels dissected, as it branched off of the large nerve root and coursed back through the foramen (between the remaining stumps of the pedicles). 
     Results 
     The sinuvertebral nerve divided variably into 3 or more branches, as expected. In every case, however, a branch of the sinuvertebral nerve was seen to course medially beneath the posterior longitudinal ligament. The posterior longitudinal ligament in this cadaver was very white and somewhat flaccid, and the space beneath it could be well visualized by only partially dividing it. Referring to  FIG.  17   , the largest medial branch of the sinuvertebral nerve was seen in every case to course directly into the basivertebral foramen, where it then divided usually into 3 to 5 smaller branches and entered the bone (see  FIG.  18   ). The dissection clearly documented that the basivertebral nerve is a branch of the sinuvertebral nerve. 
     Having successfully established the basivertebral nerve&#39;s origin as a branch of the sinuvertebral nerve and having mapped the basivertebral nerve&#39;s usual course, additional detailed dissections were undertaken to further document and illuminate these findings and to gain some understanding of the nature and prevalence of individual variants. 
     Cadaver Dissection III 
     Cadavers were positioned prone on a dissecting table. A longitudinal midline incision was made from L1 to the mid sacral level. The skin, subcutaneous fat was divided to expose the lumbar fascia. The fascial incision was carried out, also longitudinally, and the paraspinal muscles were dissected off of the spinous processes and the lamina bilaterally. The skin incision was then extended laterally from the proximal and distal end, approximately 8 cm on both sides to create the shape of an H. 
     These large flaps were then developed on both sides to allow good exposure of the spinous processes, lamina, facet joints and interlaminal spaces from L5 to L1. 
     Spinous processes were removed with rib cutters, and the lumbar lamina then removed with rongeurs and Cloward type punches. Blunt dissection allowed exposure of the dural sac. The facet joints were then completely removed bilaterally using osteotomes and rongeurs to expose the pedicle, which was viewable “end on” transected in the coronal plane. Exiting nerve roots were identified, and exposed from the axilla, to at least one cm beyond the lateral border of the pedicle, and beyond the thickened portion of the dorsal root ganglion. Following the gross exposure, superior visualization surgical loupes (3.5×) were used for visualization of the finer neurovascular structures during the remainder of the dissection. 
     Exposure of the sinuvertebral nerve was accomplished by transecting the nerve root at its base as it branched off of the dural sac. The root was then carefully and gently reflected laterally and the volar aspect inspected. In all cases, the sinuvertebral nerve was seen to exit the volar aspect of the sheath, at or immediately lateral to the distal portion of the ganglion. In many cases, other small nerves were also seen to emerge immediately distal to the dorsal root ganglion, sometimes (but not always) anastamosing with the sinuvertebral nerve. Most of the other small nerves coursed dorsally or posteriorly. Generally, only one nerve (the sinuvertebral nerve) coursed retrograde back through the foramen. 
     The details of the anatomy at each exposed level are described below: 
     Cadaver C 
     L5 left: The sinuvertebral nerve entered the epidural space before the first small branch was noted, which coursed directly caudad. The larger branch coursed cephalad to the level of the inferior border of the L5 pedicle, when a large branch travelled medially, directly to the basivertebral foramen 
     L5 Right: Two branches were seen to arise from the root, just past the thickening of the ganglion. The smaller branch coursed inferomedially before branching into two equally sized nerves just before travelling beneath the posterior longitudinal ligament. It was not possible to follow them further. The “other sinuvertebral nerve” coursed cephalomedially until dividing into two approximately equally sized branches, just medial to the posterior longitudinal ligament. One branch coursed directly medially onto the basivertebral foramen, the other coursed cephalad. 
     L4left: This sinuvertebral nerve coursed cephalomedially until it neared the edge of the posterior longitudinal ligament, where it divided into two branches. The inferior branch coursed caudad, parallel to the border of the posterior longitudinal ligament. The other coursed cephalad, immediately lateral to the border of the posterior longitudinal ligament before branching at the level of the inferior pedicle, creating a branch that coursed medially, beneath the posterior longitudinal ligament, to enter the basivertebral foramen. 
     L4 Right: This sinuvertebral nerve coursed directly medial, sending small branches cephalad and caudad shortly after entering the epidural space. The larger central branch continued medial until immediately after passing beneath the posterior longitudinal ligament, it divided into 2 nearly equal branches. One of these coursed inferiorly and medially, the other coursed cephalomedially directly to the basivertebral foramen. 
     L3 Left: The sinuvertebral nerve coursed cephalomedially to about the level of the middle of the L3 pedicle, where it trifurcated, sending one branch caudad, one branch cephalolaterally, and one branch medially. The medial branch coursed directly toward the basivertebral foramen, and divided into three smaller nerves at the basivertebral foramen, all of which entered the basivertebral foramen. 
     L3 Right: This sinuvertebral nerve had a curved course, travelling cephalomedially, trifurcating at the level of the lateral border of the posterior longitudinal ligament. A very small branch coursed directly caudad. The remaining branches were equivalent in size. One travelled cephalad, the other coursed medially and slightly inferiorly to enter the basivertebral foramen. 
     Cadaver D 
     L5 left: The sinuvertebral nerve entered the epidural space coursing medially, and did not branch until approximately 3 mm medial to the medial border of the pedicle where it began coursing cephalad. The first branch coursed medially directly to the basivertebral foramen. A second medial branch was seen that also coursed directly to the basivertebral foramen. The sinuvertebral nerve continued to course cephalad, and was not explored as it travelled past the upper border of the pedicle. 
     L5 right: Two small nerves exited the root, just beyond the pedicle and coursed back into the spinal canal. The caudad nerve coursed inferiorly. The second coursed medially for approx 0.3 cm before curving cephalad at the level of the basivertebral foramen; this nerve branched once, both branches entered the basivertebral foramen. 
     L4 Left: sinuvertebral nerve coursed into the epidural space, the first branch coursed inferiorly. The larger branch coursed cephalad. At above the level of the middle of the pedicle it split into 4 branches. Two of them coursed directly to the basivertebral foramen, and the other two coursed cephalad. 
     L4 right: The sinuvertebral nerve coursed medially for approx 3 mm, and then split into 4 branches, one coursed cephalad, one caudad and two coursed to the basivertebral foramen and entered it. 
     L3 left: the sinuvertebral nerve coursed medially for about 2 mm, then split into 4 nerves. One coursed superiorly, one coursed to the basivertebral foramen and entered it, one coursed medially (inferior to the basivertebral foramen), and one coursed caudad. 
     L3 right: The sinuvertebral nerve coursed medially approx 4 mm, a branch then travelled caudad, and another travelled obliquely caudad and medial. This branch divided into two, one coursing to the basivertebral nerve and one continuing cephalad 
     L2 left: The sinuvertebral nerve coursed medially and slightly cephalad before a branch was produced that travelled caudad. A second branch the was seen to course medially, inferior to the basivertebral foramen, the larger branch travelled very close to the basivertebral foramen and a short branch travelled medially to enter the basivertebral foramen, the continuation of this sinuvertebral nerve continued cephalad and branched again medially, above the level of the basivertebral foramen. 
     L2 right: the sinuvertebral nerve coursed cephalad and medial. The first branch coursed caudad. The second branch coursed cephalad and medial to enter the basivertebral foramen. The other branch continued cephalad. 
     Cadaver Dissection IV 
     Designs for Vision surgical loupes (6.0×) were used for visualization of the finer neurovascular structures during the remainder of the dissection. 
     Cadaver E 
     L5 left: a large sinuvertebral nerve branched more laterally than most, dividing into three branches; one coursed caudad, one cranially, and the “middle” one coursed directly to the basivertebral foramen where several small branches entered the foramen. Interestingly the larger branch continued cephalad, actually appearing to travel slightly Right of the midline. 
     L5 Right: This small sinuvertebral nerve coursed directly cephalomedially to enter the basivertebral foramen. No other branches were identified. 
     L4 left: The sinuvertebral nerve branched into three distinct nerves at the level of the foramen. One branch coursed caudad, one cephalad and the middle branch coursed directly to the basivertebral foramen. 
     L4 Right: This sinuvertebral nerve coursed very similarly to the sinuvertebral nerve on the Left. A large sinuvertebral nerve divided into 3 nearly equally sized branches at the level of the foramen. One branch curved cephalad, another curved Caudad, and the middle branch coursed directly to the basivertebral foramen. 
     L3 left: Only one small nerve was identified leaving the root and reentering the canal. This nerve coursed directly to enter the basivertebral foramen without other visible branches. 
     L3 Right: the sinuvertebral nerve was seen to enter the epidural space in a very medial direction. It divided into two branches at immediately beneath the lateral border of the dural sac. One barge branch coursed caudad. The other branch coursed cephalad, but broke before reaching the level of the inferior border of the pedicle. The broken end could not be reliably identified. 
     L2 left: the sinuvertebral nerve divided into two nearly equal branches immediately beneath the lateral border of the dural sac. One coursed caudad and medial, the other coursed directly toward the basivertebral foramen. This nerve trifurcated at the basivertebral foramen, sending one branch into the basivertebral foramen, while another branch continued cephalad. A smaller branch coursed inferomedially. 
     L2 Right: The sinuvertebral nerve abruptly separated into three branches within 2 mm of the dorsal root ganglion, at the level of the lateral border of the pedicle. 
     One branch coursed inferomedially, another cephalad, and the “middle’ one coursed directly to the basivertebral foramen, and was seen to enter it. 
     Cadaver F 
     L5 Right: The sinuvertebral nerve coursed in an almost pure medial direction, before dividing at one point into two branches. One coursed caudad one coursed nearly vertically directly to the basivertebral foramen, which it entered. The remaining branch coursed cephalad. 
     L5 Left: The nerve entered the epidural space and coursed obliquely in the direction of the basivertebral foramen, approximately 2 mm from the midline it branched, sending one branch to enter the basivertebral foramen, and another to course cephalad. No branches were seen coursing caudad, but it is possible that such were severed during the dissection. 
     L4 Left: The sinuvertebral nerve coursed medially for approx 3 mm, the first small branch coursed caudad. The larger branch of the sinuvertebral nerve coursed cephalad, at about the level of the inferior border of the pedicle where it divided into two nearly equally sized branches; one branch was seen to travel obliquely cephalad and medial to enter the basivertebral foramen. The other branch of the sinuvertebral nerve continued cephalad. 
     L4 Right: The sinuvertebral nerve coursed medial and cephalad. No branch was identified coursing caudad. At approximately the level of the inferior border of the L4 pedicle, a large branch diverged from the sinuvertebral nerve and coursed obliquely medial and cephalad and directly entered the BV foramen. The other branch continued to course cephalad. 
     L3 Left: The sinuvertebral nerve divided into two large branches while still lateral to the foramen. These branches coursed cephalad and caudad, without sending identifiable branches to the basivertebral foramen 
     L3 Right: The sinuvertebral nerve was not clearly identifiable at this level, very possibly due to disruption of the anatomy during pedicle removal. Therefore the nerve could not be traced antegrade. When dissection medially was undertaken to attempt a retrograde dissection, a “large” branch of a nerve was found to enter the basivertebral foramen from a cranial direction. Dissection at the L2 level above revealed a large “sinuvertebral nerve” nerve from immediately distal to the L2 ganglion, that coursed directly to the L3 basivertebral foramen; this nerve branched twice at the level of the L2-3 disc, sending small branches medially and laterally. The L2 nerve root also produced a “second sinuvertebral nerve” the coursed medially and centrally at the L2 level. This nerve was not explored further. 
     SUMMARY 
     Lumbar Spinal dissection was performed on a total of five cadavers with the successful approach as described. A total of 18 levels, ranging from L1 to S1 were bilaterally exposed. A total of 34 basivertebral nerves were successfully traced from their point of origin at the sinuvertebral nerve, beneath the posterior longitudinal ligament and to the point of entry into the basivertebral foramen. In every case, the innervation of the basivertebral foramen was traced to one or both (L, R) basivertebral nerve branches from the sinuvertebral nerve. In the majority of levels dissected (16118) basivertebral foramen innervations was clearly bilateral. The fragility of the branches of the sinuvertebral nerve has been noted by other authors. It is suspected that nerve breakage during dissection may have allowed some branches of the sinuvertebral nerve to have remained undetected. The typical anatomy is illustrated in  FIG.  4   , with variants as described illustrated in  FIGS.  5  and  6   . In all cases, the innervation of the vertebral body via the basivertebral foramen was from one or more medial branches of the large branch of the sinuvertebral nerve that was consistently seen coursing cephalad within the ventral epidural space. 
     Discussion 
     The paraspinal neuroanatomy (including innervation of the disc) has been extensively described. The innervation of the vertebral body has been documented as well. The neuroanatomical communication between paraspinal and intervertebral innervation and its implications has been less studied. In this study, emphasis was placed on the proximal basivertebral system, following the basivertebral nerve to its point of origin. As described above, the basivertebral nerve system originates as a medial branch of the sinuvertebral nerve. 
     The sinuvertebral nerve was specifically identified as a branch of the exiting lumbar nerve root. The sinuvertebral nerve was clearly seen to course back into the ventral epidural space, and usually was seen to branch into at least three easily identifiable branches. 
     In this study, the medial branches of the nerve were followed as they course underneath the posterior longitudinal ligament. The largest medial branches of the sinuvertebral nerve were seen to course under the posterior longitudinal ligament, and directly enter the basivertebral foramen. Such branches were seen at every level dissected. The basivertebral nerve was consistently present bilaterally. 
     Imaging and External Radiation of Basivertebral Nerve 
     Although the location of the basivertebral nerve is somewhat well known, the basivertebral nerve is a normally functioning anatomical feature that is radiolucent, so its precise location cannot be easily identified by an X-ray, angiography, or other indirect imaging methods. Since the basivertebral nerve may also be extremely thin in some embodiments, knowingly directing externally applied energy in close proximity to the basivertebral nerve, without risk to neighboring anatomy, may be problematic. 
     Several embodiments of the invention access the basivertebral nerve outside of the vertebral body, and denervate the basivertebral nerve to cut off or reduce conduction within the nerve (permanently or temporarily) to downstream locations within the vertebral body. Several embodiments of the invention predictably identify and treat the basivertebral nerve via an energy source located external to the skin (e.g., extracorporeal treatment) or external to the vertebral body of the patient (e.g., human or animal subject). 
     Several embodiments of the invention are directed to devices and methods for treating back pain by modulating (e.g., denervating, stimulating) the basivertebral nerve from an energy source located external to the body (e.g., external to the skin). While the embodiments listed below are directed to systems and methods that utilize radiation as the primary therapeutic energy modality, any type of energy capable of being directed to a focused point within the body of a patient (in one embodiment, preferably without destruction of intervening tissues and/anatomy) may be used (e.g., high-intensity or low-intensity focused ultrasound). The energy output may be dynamically controlled by changing the power intensity, the frequency, the angle of dispersion, the focus, or other dynamically controllable parameters. In some embodiments, radioactive implants may deliver energy instead of or in combination with external beam therapy. 
     For external therapy systems involving ultrasonic energy sources, the neuromodulating effects may include application of focused ultrasound energy to achieve sustained heating, sonication, and/or cavitation. In some embodiments, the focal intensity of the ultrasonic energy may range from about 100 W/cm2 to about 1 MW/cm2 , from about 1 kW/cm2 to about 10 kW/cm2 , from about 10 kW/cm2 to about 100 kW/cm2 or overlapping ranges thereof. In some embodiments, the frequency of the ultrasonic energy may range from about 500 kHz to about 10 MHz, from about 1 MHz to about 5 MHz, from about 5 MHz to about 10 MHz, or overlapping ranges thereof. In some embodiments, focused ultrasound energy may be selected to heat the tissue within the vertebral body to between about 35° C. and about 90° C., between about 40° C. and about 50° C., between about 45° C. and about 60° C., between about 50° C. and about 70° C., between about 60° C. and about 85° C., or overlapping ranges thereof. The treatment time may range from about 2 seconds to about 1 hour, from about 5 seconds to about 10 seconds, from about 10 seconds to about 30 seconds, from about 20 seconds to about 1 minute, from about 1 minute to about 5 minutes, from about 5 minutes to about 10 minutes, from about 10 minutes to about 20 minutes, from about 20 minutes to about 40 minutes, from about 30 minutes to about 45 minutes, from about 40 minutes to about 60 minutes, or overlapping ranges thereof. 
       FIGS.  19 - 21    detail the components of several embodiments of a radiotherapy system  310  configured to direct therapeutic energy to a region of the spine for purposes of modulating the basivertebral nerve.  FIG.  19    illustrates a block diagram illustrating the primary components of radiotherapy system  310 .  FIG.  20    illustrates a schematic diagram of an example radiotherapy system  310  having a moveable gantry  312 . 
     Referring to  FIG.  19   , one embodiment of an external therapy (e.g., radiotherapy) system  310  comprises a control module  314  (e.g., computer or series of computers) having a processor  316  and application programming modules  318  for controlling the delivery of energy from one or more energy sources  330 . In some implementations, the control module  314  and application programming modules  318  are configured to control and monitor output from each energy source  330  to ensure proper dosing, while simultaneously controlling motion of the energy source  330  and gantry  312  through linear drive  322  and radial drive  324  to ensure the proper delivery location of therapeutic energy into the patient  350 . The control module  314  and application programming modules  318  may also be configured to receive data (real-time or pre-acquired) from one or more imaging sources  320  (e.g., X-ray, CT, MRI, fluoroscopy, etc.). In some embodiments, external therapy (such as radiotherapy) system  310  further comprises a motion restraint  326  for immobilizing or minimizing motion of a particular spinal segment to be treated. 
       FIG.  20    illustrates a side view of one embodiment of a radiotherapy system  310  with a patient positioned for treatment. System  310  may include a table  340  that is fixed in relation to moveable gantry  312 . In one embodiment, table  340  comprises a recess  346  sized to receive lumbar support  342  of motion restraint  326 . Motion restraint  326  is shown in  FIG.  20    as a lumbar restraint for immobilizing the lumbar spine segment from motion. However, motion restraint  326  may be configured with a support for immobilizing other regions of the spine (e.g. thoracic or cervical vertebrae). In some embodiments, motion restraint  326  comprises a plurality of straps  344  that wrap around the patient torso  350  for securing the support  342  to the patient&#39;s back adjacent to the lumber spine. In one embodiment, the motion restraint  326  is further configured to lock into the recess  346  so that the support  342  does not move with respect to the table  340 . 
     In one embodiment, one or more radiation sources  330  are disposed in a moveable gantry  312  that is allowed to translate in (x, y, z) directions via linear drive  322 .  FIG.  21    shows a sectional view of one embodiment of the radiotherapy gantry  312 . The gantry  312  comprises a tubular frame  334  configured to house one or more radiation sources  330 . Each of the radiation sources may be embedded into the frame and configured to direct radiation energy through dedicated collimators  332  so as to focus the radiation beams  335  at the center-point of the gantry Cp. 
     In  FIG.  21   , the gantry  312  is shown centered about the target treatment site T (e.g., the center-point of the gantry Cp is shown coincident with the treatment target T). In some embodiments, imaging sources  320  are used (optionally in conjunction with images obtained from pre-acquired patient imaging) to help center the gantry  312  at the treatment location T (shown in  FIG.  21    as the vertebral body  356  of L4 vertebra  352 ). 
     In accordance with several embodiments, gantry  312  is shown in  FIG.  21    as housing eight radially spaced-apart radiation sources  330 . However, the number of radiation sources  330  may vary from one to several hundred, depending on the type of radiation sources being used. 
     In accordance with several embodiments, in order to treat the basivertebral nerve of vertebral body  352 , which is deep within the body of the patient, the radiation  335  penetrates the intervening healthy tissue in order to irradiate and modulate (e.g., denervate) the basivertebral nerve. In several embodiments, the treatment is performed without exposing large volumes of healthy tissue to harmful doses of radiation, thereby resulting in reduced recovery periods for the patient. In some embodiments, the patient is treated with ionizing radiation and treatment protocols so as to expose the target tissue to a dose of radiation that results in the desired cell modification, while keeping the exposure of healthy tissue to a minimum. 
     In order to avoid excessive doses being applied to healthy tissue, in some embodiments, the incident direction may be varied throughout the treatment period (e.g., by rotating gantry  312  with the various beams of radiation  335  each converging on a single point). Radial drive  324  may thus be employed to rotate the gantry  312  about the z-axis as shown in  FIGS.  20  and  21   . 
     In some embodiments, a large number of radiation sources  330  (e.g., from about 200 to about 300, from about 50 to about 100, from about 100 to about 200, overlapping ranges thereof, over 200) may be employed at a lower dose that individually have a negligible effect on intervening tissue. The single center point (Cp) may thereby receive a full dose, while the surrounding areas receive only a minimal dose. It is also possible to employ both a combination of multiple sources  330  and a rotating gantry  312 . 
     Radiation sources  330  may comprise one of a number of different types, e.g., particle beam (proton beam therapy) sources, cobalt-60 based (photon or gamma-ray sources such as found in the Gamma Knife® technology), linear accelerator based (linac source such as that used in the CyberKnife® or Novalis® Tx technology). Gamma Knife® sources may produce gamma rays from the decay of Co-60 at an average energy of 1.25 MeV. The radiation sources  330  may include over  200  sources arrayed to deliver a variety of treatment angles. In some embodiments, linear accelerators emit high energy X-rays, usually referred to as “X-ray therapy” or “photon therapy.” The x-rays are produced from the impact of accelerated electrons striking a high z target (usually tungsten). Linear accelerators therefore can generate any number of energy x-rays (e.g., 6 MV photons). For linear accelerators, the gantry generally moves in space to change the delivery angle. 
     Referring now to  FIGS.  22  and  23   , which illustrate the anatomy of a typical lumbar vertebra  352 , the treatment target (e.g., basivertebral nerve) is a normally functioning anatomical feature that is radiolucent, so it generally cannot be seen or identified by an X-ray, angiography, or other indirect imaging methods. Accordingly, several embodiments of the invention use a novel approach for determining and verifying the target treatment site T. 
       FIGS.  22  and  23    illustrate side and top views, respectively, of a lumbar vertebra  312 , showing vertebral body  356 , and spinous process  358 , in addition to the path  354  and plexus  362  of the basivertebral nerve. One or more basivertebral nerves  354  enter the vertebral body  356  through the basivertebral foramen  355 , which is a conical opening emanating from the spinal canal  360 , and generally penetrate the posterior cortex of the vertebral body  356  along the midline of the vertebral body  356 . The basivertebral nerves  354  enter the vertebral body  356  at the basivertebral foramen  355 , continue distally (anteriorly) through the vertebral body, and arborize at plexus  362  to innervate the vertebral body  356  down to and including the endplates 
     In some embodiments, the target region T of the basivertebral nerve  354  is located within the cancellous portion of the bone (e.g., to the interior of the outer cortical bone region), and at or proximal to the junction or plexus  362  of the basivertebral nerve  354  having a plurality of branches. In some embodiments, treatment in this region (at or proximal to the junction or plexus  362 ) is advantageous because only a single portion of the basivertebral nerve  354  need be effectively treated to denervate (temporarily or permanently) the entire downstream nerve system. In contrast, treatment of the basivertebral nerve  354  at locations more downstream than the junction  362  may require the denervation of each individual branch. 
     Treatment in accordance with several embodiments of the invention can be effectuated by focusing energy  335  in the target region T of the vertebral body  356  located between 60% (point C) and 90% (point A) of the distance between the posterior and anterior ends of the vertebral body. Point A will often reside in the basivertebral foramen  355 , and therefore energy directed to that region may not be as contained (basivertebral foramen  355  opens to the vertebral canal  360 , containing sensitive anatomy such as the spinal chord) as when directed into the vertebral body at points B or C (which are surrounded at all sides by bone). Point C may run the risk of being downstream from the nerve junction. 
     In various embodiments, treatment can be effectuated by focusing in the region of the vertebral body located at a region that is more than 1 cm from the outer cortical wall of the vertebral body, within a region that is centered at or about 50% of the distance from the posterior outer cortical wall of the vertebral body to the anterior outer cortical wall, and/or within a region that is between 10% and 90% (e.g., between about 10% and about 60%, between about 20% and about 80%, between about 35% and about 65%, between about 25% and about 75%, between about 10% and about 55%, between about 30% and about 70%, or overlapping ranges thereof) of the distance from the posterior outer cortical wall of the vertebral body to the anterior outer cortical wall. 
     In accordance with several embodiments, because the basivertebral nerve is not visible from radiographic imaging, a radiographically identifiable reference point RPb may be advantageously established to determine a target treatment site T that corresponds with the correct location within the vertebral body. In  FIGS.  20    through  FIG.  24   , reference point RPb is shown at the tip of the spinous process  358 . Other physical landmarks may also be used without departing from the spirit and/or scope of the disclosure. The table  340  and/or motion restraint  326  may have a radiographically identifiable marker to establish external reference point RPr, which may be used for identifying the target T with respect to the treatment source  330  focal point/center point Cp. 
       FIG.  24    illustrates a flow diagram of one embodiment of a method  400  for identifying and treating back pain through radiotherapy of the basivertebral nerve  354 . In one embodiment, method  400  is carried out with use of radiotherapy system  31  O; however other external therapy/surgery systems may be used to perform method  400 . 
     First, imaging data (also called image data) of the target anatomy (e.g., vertebra  352 ) is acquired at pretreatment imaging step  402 . Image data (e.g. real-time or preacquired x-rays) may be obtained from one or more imaging sources  320 , and/or from an outside imaging source (e.g., x-ray, CT, MRI, OCT, angiography, Doppler, ultrasound, etc.). The image data may be used to determine coordinates and dimensions of the target vertebra  312  used in acquiring or identifying the target location or treatments site T. In some embodiments, imaging is not performed. In some embodiments, imaging may be supplemented or replaced by non-imaging techniques that facilitate targeted treatment. In one embodiment, imaging is performed using the same system (e.g., transducer) that provides therapy. 
     In one embodiment, patient feedback may be obtained through a series of steps  404  through  418  to verify that source center point Cp is correctly positioned at the target treatment site T. In one embodiment, this verification is achieved by determining a pretreatment dose location (PDL) at step  404 , which corresponds to the physician&#39;s (and/or other medical practitioner&#39;s) best estimate for the target basivertebral nerve location T, and delivering one or more identification doses. In another embodiment, the pretreatment dose location PDL is assumed to be the target location T, and the treatment dose TD is delivered at step  420 , effectively skipping feedback steps  404  through  418 . 
     In accordance with several embodiments, determining the pretreatment dose location PDL at step  404  generally involves analysis of data acquired from pretreatment imaging step  402 . Reference points RPb and RPr (shown in  FIGS.  20  through  23   ) may first be identified to aid in the determination of the treatment target. Once the reference point RPb on the target vertebra  352  is identified, the pretreatment dose location PDL corresponding to expected target T (Xt, Yt, Zt) may be set according to a calculated coordinate distance (e.g., corresponding to a predicted basivertebral nerve location) from the reference point RPb (Xr, Yr, Zr). For example, target T may be at coordinate (Xr+O, Yr+Yd, Zr+Zd), where distances Yd and Zd are computed based at least in part on the pre-acquired imaging data of the anatomy and one or more predetermined metrics. For example, distance Yd may be calculated according to the Y coordinate point corresponding to 75% of the distance from the anterior end of the vertebral body  356  to the posterior end of the vertebral body  356 . Distance Zd may be calculated according to the Z coordinate point corresponding to a midline of vertebral body  356 . Since the tip of the spinous process  358  generally corresponds to the X coordinate of the basivertebral nerve  354 , the reference coordinate Xr will typically be equal to the target coordinate Xt. In some embodiments, reference RPr on table  340  may be used as the starting point from which motion of the gantry  312  is based to center the source  330  about the pretreatment dose location PDL (e.g., PDL=Cp). 
     In one embodiment, at step  408 , an identification dose is delivered to the pretreatment dose location PDL. This identification dose is generally a fraction of the treatment dose TD, and may be prescribed to elicit some response from the patient relating to the patient&#39;s pain. At step  410 , patient feedback is acquired to verify a change in the sensation of pain within the region. The patient&#39;s change in pain sensation may be positive (e.g., temporarily alleviate or lessen pain via numbing effect, etc.) or negative (e.g., the small dose aggravates the nerve ends, thereby causing more pain). 
     If no change in pain is experienced by the patient  350 , the source  330  center point Cp may be adjusted to a new pretreatment dose location (PDLx) at step  414 . In some embodiments, an additional identification dose is then delivered at step  416 . Patient feedback is then elicited for some change in sensation relating to the patient&#39;s pain at step  418 . If no change in pain is still experienced by the patient  350 , the source  330  center point Cp may be adjusted to yet another pretreatment dose location (PDLx) at step  414 . In some embodiments, the loop continues in a scanning fashion until the patient identifies a change in pain sensation, thus verifying that the target dose location T is the last treatment dose location (PDL) at step  412 . 
     Next, in accordance with several embodiments, the treatment dose TD is delivered to the target T. Embodiments with radial drive  324  may be operated to change the delivery angle during treatment and minimize the dose to non-target tissues. The treatment dose TD is generally prescribed before treatment, and can be a factor of the patient&#39;s age, anatomy, desired treatment volume  364  (see  FIG.  22   ), etc. In some embodiments, the treatment dose is configured to denervate the basivertebral nerve  354  to inhibit transmission of pain signals from within the vertebral body  356 . 
     In one embodiment, the prescribed treatment dose is configured to deliver therapeutic treatment that is targeted to block nerve conduction without ablating the nerve, e.g., thermal treatment is delivered to the nerve that results in denervation of the basivertebral nerve  354  without necrosis of tissue. This denervation without ablation or necrosis may be achieved via delivery of a lesser amount of energy or agent to the tissue site (either in the form of less exposure time, concentration, intensity, etc.) than is required for ablation, but an amount sufficient to achieve some amount of temporary or permanent denervation. 
     In one embodiment, the treatment dose for delivery of gamma radiation delivered to the patient will typically range between 10 Gy and 70 Gy (e.g., between about 10 Gy and about 30 Gy, between about 20 Gy and about 50 Gy, between about 30 Gy and about 60 Gy, between about 40 Gy and about 70 Gy, or overlapping ranges thereof). However, because the treatment region is contained within the large bony mass vertebral body  356 , higher doses may be contemplated, as there is little risk to surrounding tissues that are more vulnerable. The dose may be varied based on the treatment volume  364 , or other variables, such as treatment time and dose concentration. A prescription of 35 instances of a 2 Gy dose might be replaced by 15 instances of a 3 Gy dose, a technique known as “hypofractionation.” Taken to its logical extreme, this dose might be replaced with a single 45 Gy dose if the dosage delivered to healthy tissue can be reduced significantly. 
     In several embodiments, the identification dose used in steps  408  through  416  is generally a much smaller dose than treatment dose TD, so as not to damage healthy tissue. An example dose may range from 0.5 Gy to 5 Gy (e.g., between about 0.5 Gy and about 2 Gy, between about 1 Gy and about 2.5 Gy, between about 1.5 Gy and about 3 Gy, between about 2 Gy and about 5 Gy, or overlapping ranges thereof. However, this range may also change based on considerations such as anatomy, patient, etc. 
     In some embodiments, one or more radioactive implants are used to deliver radiotherapy instead of or in combination with external beam therapy. The one or more radioactive implants may be inductively powered or activated from outside the body over time (e.g., periodically or as desired or required). In some embodiments, the radioactive implants include an internal battery. The radioactive implants may deliver radioactive therapy over time without additional activation. The radioactive implants may be permanent or removable. In some embodiments, a radioactive implant comprises a plurality of radioactive sources or a plurality of radioactive seeds. In accordance with several embodiments, treatment time is subject to rate of radioactive decay of the radioactive implants. In some embodiments, the radiotherapy is delivered over a matter of minutes (e.g., 10 to 60 minutes, 20 to 40 minutes, 15 to 50 minutes, or overlapping ranges thereof), a matter of hours (e.g., 1 to 24 hours, 2 to 6 hours, 8-12 hours, or overlapping ranges thereof), a matter of days (e.g., 1 to 3 days, 2 to 8 days, 2 to 4 days, or overlapping ranges thereof), a matter of months (e.g., 1 to 12 months, 2 to 6 months, 4 to 10 months, 3 to 9 months, or overlapping ranges thereof), or a matter of years (e.g., 1 to 10 years, 2 to 6 years, 3 to 6 years, or overlapping ranges thereof). 
     Referring now to  FIG.  25   , in one embodiment, the application programming modules  318  may be configured to acquire real-time imaging data from imaging sources  320  to provide a motion-driven delivery of the treatment dose at step  420 . In some embodiments, this ensures that the source Cp is delivering the dose to the target T, even in the event of incidental patient motion. An incremental treatment dose (e.g., an amount TDx equal to total treatment dose TD divided by number of increments) is delivered at step  432 . At step  434 , the routine determines if the total prescribed dose TD has been delivered. If yes, the routine ends at step  436 . If not, the treatment location is imaged with respect to table  340  or restraint support  342  at step  438  (e.g., vertebra reference point RPb with respect to reference point RPr). At step  440 , the distanced between source center point Cp and newly acquired target T data is calculated. The distanced is then compared against a threshold value Th at step  442 . The treatment dose TD may be adjusted according to the desired sensitivity of the system  400 . If distance d is less than value Th, the routine returns back to step  432  to deliver another incremental dose TDx. If distance d is greater than value Th, the source  330  (e.g., via linear motion of gantry  312 ) is translated at step  444  such that CP=T, and then the routine returns back to step  432  to deliver another incremental dose TDx. 
     While motion tracking dosing routine  420  of  FIG.  25    may be used in place of physical restraint  326 , in accordance with several embodiments, it is generally preferred to use the motion tracking in combination with restraint  326  to ensure delivery of energy to the proper target location T. 
     Although the treatments and therapies were described with reference to intraosseous nerves (e.g., basivertebral nerves) within the spine, the disclosed methods and systems may be used to modulate (e.g., ablate, stimulate) nerves within other bones in other locations of the body. 
     Conditional language, for example, among others, “can,” “could,” “might,” or “may,” unless specifically stated otherwise, or otherwise understood within the context as used, is generally intended to convey that certain embodiments include, while other embodiments do not include, certain features, elements and/or steps. 
     Although certain embodiments and examples have been described herein, aspects of the methods and devices shown and described in the present disclosure may be differently combined and/or modified to form still further embodiments. Additionally, the methods described herein may be practiced using any device suitable for performing the recited steps. Some embodiments have been described in connection with the accompanying drawings. However, it should be understood that the figures are not drawn to scale. Distances, angles, etc. are merely illustrative and do not necessarily bear an exact relationship to actual dimensions and layout of the devices illustrated. Components can be added, removed, and/or rearranged. Further, the disclosure (including the figures) herein of any particular feature, aspect, method, property, characteristic, quality, attribute, element, or the like in connection with various embodiments can be used in all other embodiments set forth herein. 
     For purposes of this disclosure, certain aspects, advantages, and novel features of the inventions are described herein. Embodiments embodied or carried out in a manner may achieve one advantage or group of advantages as taught herein without necessarily achieving other advantages. The headings used herein are merely provided to enhance readability and are not intended to limit the scope of the embodiments disclosed in a particular section to the features or elements disclosed in that section. The features or elements from one embodiment of the disclosure can be employed by other embodiments of the disclosure. For example, features described in one figure may be used in conjunction with embodiments illustrated in other figures. 
     Embodiments of the invention may be described with reference to flowchart illustrations of methods and systems according to embodiments of the invention, and/or algorithms, formulae, or other computational depictions, which may also be implemented as computer program products. In this regard, each block or step of a flowchart, and combinations of blocks (and/or steps) in a flowchart, algorithm, formula, or computational depiction can be implemented by various means, such as hardware, firmware, and/or software including one or more computer program instructions embodied in computer-readable program code logic. As will be appreciated, any such computer program instructions may be loaded onto a computer, including without limitation a general purpose computer or special purpose computer, or other programmable processing apparatus to produce a machine, such that the computer program instructions which execute on the computer or other programmable processing apparatus create means for implementing the functions specified in the block(s) of the flowchart(s). 
     Accordingly, blocks of the flowcharts, algorithms, formulae, or computational depictions support combinations of means for performing the specified functions, combinations of steps for performing the specified functions, and computer program instructions, such as embodied in computer-readable program code logic means, for performing the specified functions. It will also be understood that each block of the flowchart illustrations, algorithms, formulae, or computational depictions and combinations thereof described herein, can be implemented by special purpose hardware-based computer systems which perform the specified functions or steps, or combinations of special purpose hardware and computer-readable program code logic means. 
     Furthermore, these computer program instructions, such as embodied in computer-readable program code logic, may also be stored in a computer-readable memory that can direct a computer or other programmable processing apparatus to function in a particular manner, such that the instructions stored in the computer-readable memory produce an article of manufacture including instruction means which implement the function specified in the block(s) of the flowchart(s). The computer program instructions may also be loaded onto a computer or other programmable processing apparatus to cause a series of operational steps to be performed on the computer or other programmable processing apparatus to produce a computer-implemented process such that the instructions which execute on the computer or other programmable processing apparatus provide steps for implementing the functions specified in the block(s) of the flowchart(s), algorithm(s), formula(e), or computational depiction(s). 
     Although the description above contains many details, these should not be construed as limiting the scope of the invention but as merely providing illustrations of some of the embodiments of this invention. Therefore, it will be appreciated that the scope of the invention fully encompasses other embodiments which may become obvious to those skilled in the art, and that the scope of the invention is accordingly to be limited by nothing other than the appended claims, in which reference to an element in the singular is not intended to mean “one and only one” unless explicitly so stated, but rather “one or more.”