Patent Publication Number: US-9848934-B2

Title: Thermochemical ablation of bodily tissue

Description:
CROSS-REFERENCE TO RELATED APPLICATION(S) 
     This application is a continuation of U.S. patent application Ser. No. 14/081,001 filed on Nov. 15, 2013, (U.S. Pat. No. 8,926,586) and entitled “Thermochemical Ablation of Bodily Tissue,” which is a continuation of U.S. patent application Ser. No. 13/716,410 filed on Dec. 17, 2012 (U.S. Pat. No. 8,585,691) and entitled “Thermochemical Ablation of Bodily Tissue,” which is a continuation of U.S. patent application Ser. No. 12/528,015 filed on Jan. 26, 2010 (U.S. Pat. No. 8,343,095) and entitled “Thermochemical Ablation of Bodily Tissue,” which is a National Stage application under 35 U.S.C. §371 and claims benefit under 35 U.S.C. §119(a) of International Application No. PCT/US2008/054556, filed Feb. 21, 2008, and entitled “Thermochemical Ablation of Bodily Tissue”, which claims priority to U.S. Application No. 60/891,793 filed on Feb. 27, 2007 and entitled “Thermochemical Ablation of Bodily Tissue.” The entire disclosures of these earlier applications are incorporated herein by reference. 
    
    
     TECHNICAL FIELD 
     This document relates to delivery of chemical reagents to targeted bodily tissue, for example, to provide thermochemical ablation therapy. 
     BACKGROUND 
     A number of ablation treatments have been used to treat tumors or other tissue in a patient&#39;s body. In some cases, ablation therapy may be used to treat tumors that are not responsive to chemotherapy or other techniques. For example, primary liver cancer or hepatocellular carcinoma (HCC) is an aggressive neoplasm that may not respond well to intravenous chemotherapy. 
     The choice of treatment for HCC normally depends on severity of underlying liver disease, size and number of lesions, location of lesions, ability to detect them with MRI, non-contrast or contrast CT, or ultrasound, and local expertise. Conventionally, physicians have employed RF ablation or microwave ablation to destroy the tumor tissue with heat, combined heating with coadministration of liposomes containing a drug, cryoablation to freeze a tumor, hepatic arterial drug infusion, bland arterial embolization, chemotherapy combined with arterial embolization, selective internal radioembolization using radioactive labeled iodized oil or radioactive microspheres as the embolic agent, external beam radiation therapy, or direct injection of a single agent (e.g., ethanol, acetic acid, hydrochloric acid, hot saline, or sodium hydroxide) to ablate the tumor. 
     One low cost and less invasive method is percutaneous injection of one of either ethanol or acetic acid. Although high-cost RF or microwave ablation systems are generally not employed with this method, conventional single-agent injections have raised concerns. The injection of a single agent such as acetic acid may increase the acid load in the patient, which cause toxicity problems and possibly renal failure. The injection of a single agent such as ethanol can also cause toxicity problems. To regulate the acid load or other toxicity problems from the injections of the single chemical agent, the dosage for each session is usually limited. Smaller dosages of the agent may generally limit the physician&#39;s ability to treat anything other than smaller tumors. 
     SUMMARY 
     Some thermochemical ablation techniques may provide minimally invasive ablation of solid tumors such as liver cancer, lung cancer, renal cancer, breast cancer, prostate cancer, sarcomas, metastatic disease, or the like. These ablation techniques may induce chemical reactions to generate heat for ablation energy (e.g., employing chemical reaction energy rather than electrical energy, magnetic energy, or direct chemical toxic effects). Such chemical reactions may be induced by mixing at least one acid reagent and at least one base reagent, which can neutralize the acid load applied to the patient during the procedure. In some circumstances, the concentration of the base reagent or the acid reagent can be selected so as to partially neutralize the acid or base load while generating heat energy, thereby providing heated solution with a limited and safe level of remaining acid or base load. Accordingly, the techniques described herein may permit a physician to simultaneously infuse at least two thermochemical ablation reagents without mixing the reagents until the reagents reach the distal portion of the delivery cannula. 
     In some embodiments, a thermochemical ablation system may include a percutaneous fluid delivery cannula comprising first and second lumens extending from a proximal portion to a distal portion. The distal portion may have a first side port in fluid communication with at least the first lumen and a second side port in fluid communication with at least the second lumen. The system may also include a first reservoir that contains a first thermochemical ablation reagent so as to communicate the first thermochemical ablation reagent through the first lumen to the distal portion of the percutaneous fluid delivery cannula. The portion of the first thermochemical ablation reagent can be deliverable out of the first side port. The system may further include a second reservoir that contains a second thermochemical ablation reagent so as to communicate the second thermochemical ablation reagent through the second lumen to the distal portion of the percutaneous fluid delivery cannula. The portion of the second thermochemical ablation reagent can be deliverable out of the second side port to provide simultaneous radial dispersion and mixing of the first and second thermochemical ablation reagents at the distal portion. 
     Particular embodiments of a device to ablate bodily tissue may include a multi-lumen thermochemical ablation cannula to simultaneously infuse at least two thermochemical ablation reagents into targeted tissue proximate a distal portion of the cannula. The distal portion of the cannula may include a plurality of fluid ports to dispense at least two thermochemical ablation reagents and thereby mix the at least two thermochemical ablation reagents proximate a distal portion of the cannula. When the at least two thermochemical ablation reagents are dispensed from the plurality of fluid ports, the thermochemical ablation reagents can mix with one another to generate an exothermic chemical reaction sufficient to ablate tissue. 
     In some embodiments, a method for thermochemical ablation of targeted tissue may include delivering a first thermochemical ablation reagent through a first lumen of a percutaneous injection needle. The method may also include delivering a second thermochemical ablation reagent through a second lumen of the percutaneous injection needle. The method may further include simultaneously infusing first and second thermochemical ablation reagents into targeted tissue to radially disperse and mix the first and second thermochemical ablation reagents at a distal portion of the injection needle. 
     Some or all of these embodiments may provide one or more of the following advantages. First, the thermochemical ablation techniques may provide minimally invasive ablation of solid tumors (e.g., liver cancer, lung cancer, renal cancer, breast cancer, prostate cancer, sarcomas, or the like) or other tissues including varicoceles, varicose veins, or the like. Such techniques may be useful, for example, to treat patients who are not surgical candidates due to the nature of the tumors or other intervening factors. Second, the thermochemical ablation techniques may induce chemical reactions to generate heat either to be the primary ablation source or to augment another ablation source (e.g., RF ablation, microwave ablation, denaturant sources such as sclerosants, detergents, or urea, or other ablation sources). Third, the chemical reactions may be induced by mixing at least one acid reagent and at least one base reagent, thereby reducing or eliminating the acid or base load applied to the tissue. Because the acid or base load is reduced or eliminated, a larger dose of reagents may be applied without causing toxicity problems. Furthermore, in some embodiments, the salt byproducts from the mixing of the first and second thermochemical ablation reagents can be highly hyperosmolar, thereby creating a local environment incompatible with cell survival in the treated tissue after the heat energy is applied. Fourth, some of the systems and devices described herein may be manufactured without high-cost components such as RF ablation probes. Fifth, the thermochemical ablation techniques described herein may be used to treat larger tumors in a lower number of treatment sessions, thereby adding convenience to the patient. Sixth, the thermochemical ablation process can be monitored in real-time using medical imaging systems, such as ultrasound imaging devices. Moreover, in some embodiments, the thermochemical ablation process can be monitored in an MRI setting without the need for specialize (high-cost), MRI-compatible alloys in the delivery device. Seventh, the devices described herein permit a physician to simultaneously infuse at least two thermochemical ablation reagents without mixing the reagents until the reagents reach the distal portion of the delivery cannula. As such, some embodiments of the delivery device can be used to provide the ablation heat energy to internal body tissue without the requirement for outer layers of thermal insulation that may otherwise increase the outer size of the delivery device (and the delivery pathway through the tissue). Eighth, the delivery cannula may include a number of side ports that provide radial dispersion of the reagents when exiting the cannula, thereby promoting mixing (e.g., more turbulence) and distributing the ablation heat energy in a more even manner. Moreover, the first and second thermochemical ablation reagents can provide an ablative effect that causes more even shaping in the treated area (as compared to a direct injection of acetic acid or ethanol) due to the conductive effects of heat into the surrounding tissue. Ninth, in some circumstances, a portion of the first and second reagents can mix with one another within the distal portion of the cannula before dispensation into the targeted tissue. By mixing at least a portion of the first and second thermochemical ablation reagents in the distal portion, some portion of the dispensed fluid can be heated from the exothermic chemical reaction immediately before dispensation into the targeted tissue. 
     The details of one or more embodiments of the invention are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the invention will be apparent from the description and drawings, and from the claims. 
    
    
     
       DESCRIPTION OF DRAWINGS 
         FIG. 1  is a section view of a thermochemical ablation system, in accordance with some embodiments. 
         FIG. 2  is a cross-sectional view of a portion of a delivery cannula for a thermochemical ablation system, in accordance with some embodiments. 
         FIG. 3  is a cross-sectional view of a portion of an alternative delivery cannula for a thermochemical ablation system, in accordance with some embodiments. 
         FIG. 4  is a cross-sectional view of a portion of yet another alternative delivery cannula for a thermochemical ablation system, in accordance with some embodiments. 
         FIG. 5  is a section view of an alternative embodiment of a thermochemical ablation system. 
     
    
    
     Like reference symbols in the various drawings indicate like elements. 
     DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS 
     A thermochemical ablation system may employ minimally invasive techniques to ablate solid tumors or other targeted tissue. These ablation techniques may induce chemical reactions to generate heat for ablation energy. Such chemical reactions may be induced by mixing at least one acid reagent and at least one base reagent, which can neutralize or otherwise reduce the acid or base load applied to the patient during the procedure. Because the acid or base load is reduced or eliminated, a larger dose of reagents may be applied and a greater level of ablation energy may be achieved without causing toxicity buildup in the patient. In some embodiments, a thermochemical ablation system enables a physician to simultaneously infuse at least two thermochemical ablation reagents without mixing the reagents until the reagents reach the targeted tissue. 
     The thermochemical ablation techniques described herein can be used to treat solid tumors that arise in number of circumstances, including liver cancer, lung cancer, renal cancer, breast cancer, prostate cancer, sarcomas, or the like. These techniques may be useful, for example, to treat patients who are not surgical candidates due to the nature of the tumors or other intervening factors. For example, some patients with HCC or other types of liver cancer are not candidates for surgery. The thermochemical ablation system described herein may be effective in the treatment of such liver cancer in a manner that is relatively convenient to the patient (e.g., possibly reducing the number of treatment sessions) and relatively cost-effective for the medical care provider (e.g., not necessarily requiring high-cost equipment such as RF ablation probes or the like). 
     Referring to  FIG. 1 , a thermochemical ablation system  100  is capable of infusing thermochemical ablation reagents into targeted tissue  50  to induce a chemical reaction and thereby ablate the tissue  50 . The system  100  includes a first fluid reservoir  110  and a second fluid reservoir  120  that are in fluid communication with a thermochemical ablation device  130 . The first reservoir  110  may include a first thermochemical ablation reagent  115  (such as an acid reagent), and the second reservoir  120  may include a second thermochemical ablation reagent  125  (such as a base reagent). Also, each of the reservoirs  110  and  120  includes an actuator  112  and  122  that can be adjusted to provide a dispensing force to the reagents  115  and  125 . Accordingly, the first and second reservoirs  110  and  120  can be actuated to deliver both reagents  115  and  125  to a proximal portion  132  of the fluid delivery device  130 , which then passes the reagents  115  and  125  to a distal portion  134  of the device  130 . In this embodiment, the first actuator  112  and the second actuator  122  are coupled to one another with a coupling  119  so that both actuators  112  and  122  can be simultaneous adjusted. For example, a user may apply a force to the coupling  119  to contemporaneously adjust the actuators  112  and  122 , which causes the first and second reagents  115  and  125  to be simultaneously delivered to the device  130 . In another example, a physician or other user may selectively activate a computer-controlled mechanism that acts upon the coupling  119  to provide the adjustment force. Such a computer-controlled mechanism may provide for accurate dosages of the reagents  115  and  125  delivered from the reservoirs  110  and  120 . In other embodiments, the first and second reservoirs  110  and  120  may not be coupled to one another, and the actuators  112  and  122  may be separately adjusted to dispense the reagents simultaneously or in selected sequence. 
     In this embodiment, the thermochemical ablation device  130  includes a multi-lumen cannula  140  that can simultaneously infuse the first and second thermochemical ablation reagents  115  and  125  into the targeted tissue  50  proximate the distal portion  134 . In particular, the cannula  140  includes a first lumen  142  in fluid communication with the first reservoir  110  to deliver the first thermochemical ablation reagent  115  to the distal portion  134 . Also, the cannula  140  includes a second lumen  144  in fluid communication with the second reservoir  120  to deliver the second thermochemical ablation reagent  125  to the distal portion  134 . The distal portion  134  of the cannula  140  may include a plurality of fluid ports  145   a - b  to radially disperse the first and second thermochemical ablation reagents  115  and  125  and thereby mix the reagents  115  and  125  in the region proximate the distal portion  134 . It should be understood that, in other embodiments, three or more reservoirs may be used to deliver three or more thermochemical ablation reagents to the targeted tissue  50 . In such circumstances, thermochemical ablation device may include a multi-lumen cannula having three or more lumens, each of which being in fluid communication with an associated fluid reservoir. 
     Still referring to  FIG. 1 , this embodiment of the fluid delivery device  130  includes a cannula  140  in the form of a percutaneous injection needle. For example, the cannula  140  may includes a generally rigid needle body  146  having an outer diameter of about 0.135 inches or less, about 0.120 inches to about 0.008 inches, and about 0.072 inches to about 0.028 inches. The needle body  146  may comprise stainless steel or another generally rigid material that is suitable for percutaneous insertion through the patient&#39;s skin  40 . Furthermore, the distal tip portion of the cannula  140  may include a pointed tip so as to facilitate penetration through the skin  40  and toward the targeted tissue  50 . The cannula  140  may also include an internal tube  147  that passes through the needle body  146 . In this embodiment, the internal tube  147  comprises a second, smaller needle body that is generally coaxial with the outer needle body  146 , thereby defining the first lumen  142  within the second lumen  144 . It should be understood that, in other embodiments, the first and second lumens  142  and  144  may be configured to have a side-by-side arrangement (refer, for example, to  FIG. 3 ). In such circumstances, the first and second lumens  142  and  144  may be defined by two bores that are formed through the outer needle body  146  (e.g., without using a centrally located internal tube  147 ). 
     In some embodiments, the fluid delivery device  130  may be packaged as part of a thermochemical ablation kit, which the physician or other user can use without the need to further assemble any components of the device  130 . For example, the fluid delivery device  130  may be manufactured so that outer needle body  146 , the inner tube  147 , and a valve device  135  are fully assembled and packaged into the kit. Also, the cannula  140  can be manufactured so that the first lumen  142  is in fluid communication with side ports  145   a  and the second lumen  144  is in fluid communication with the side ports  145   b  (described in more detail below, for example, in connection with  FIGS. 2-4 ). In these circumstances, the physician or other user can readily unpackage the fluid delivery device  130  from the kit and thereafter connect both the first fluid line  136  of the fluid delivery device  130  to the first reservoir  110  and the second fluid line  137  to the second reservoir  120 . Such fluid line connections permit the first and second reservoirs  110  and  120  to be in fluid communication with the first and second lumens  142  and  144 . 
     As shown in  FIG. 1 , the distal portion  134  of the fluid delivery device  130  may include one or more side ports  145   a - b  through which the first and second reagents  115  and  125  are dispensed into the targeted tissue  50 . The side ports  145   a - b  may be oriented so that the thermochemical ablation reagents  115  and  125  are radially dispersed from the distal portion  132 . Such radial dispersion of the thermochemical ablation reagents may provide improved mixing of the reagents  115  and  125  upon exiting the fluid delivery device  130  (e.g., due to increased turbulence). Furthermore, the radial dispersion through the side ports  145   a - b  can more evenly distribute the heat generated by the mixing of the reagents  115  and  125 . 
     The first set of side ports  145   a  may be in fluid communication with the first lumen  142  so that the first thermochemical ablation reagent  115  is evacuated from the side ports  145   a  when the coupler  119  (and first actuator  112 ) is adjusted. Likewise, the second set of side ports  145   b  may be in fluid communication with the second lumen  144  so that the second thermochemical ablation reagent  125  is evacuated from the side ports  145   b  when the coupler  119  (and second actuator  112 ) is adjusted. Accordingly, the fluid delivery device  130  provides for simultaneous infusion of the first and second reagents  115  and  125  into the targeted tissue  50 , during which the thermochemical ablation reagents  115  and  125  mix with one another to cause an exothermic chemical reaction. If the first and second reagents  115  and  125  are to be infused in different proportions, the first reservoir  110  may have a different configurations (e.g., different cross-sectional areas) so that different amounts of fluid are dispensed when the actuators  112  and  122  are simultaneously adjusted (e.g., using the coupler  119 ). In some embodiments, the concentration of the base reagent or the acid reagent can be selected so as to fully neutralize the acid and base load applied to the targeted tissue  50  after the thermochemical ablation reaction. In other embodiments, the concentration of the base reagent or the acid reagent can be selected so as to partially neutralize the acid or base load while generating heat energy, thereby providing heated solution with a limited and safe level of remaining acid or base load. 
     The heat generated from this chemical reaction may be sufficient to ablate at least a portion of the targeted tissue  50  surrounding the distal portion  134  of the fluid delivery device  130 . Because the fluid delivery device  130  infuses two reagents that chemically react with one another (rather than direct injection of a single acidic reagent), the byproducts of the chemical reaction may include greater heat generation with lower acid (or base) load toxicity. For example, in some embodiments, the fluid delivery device  130  can infuse both an acid reagent and a base reagent to create a larger lesion in the targeted tissue  50  (e.g., larger than would otherwise be obtained by direct injection acetic acid alone) while simultaneously reducing the acid load, whether by lesion expansion or by a thermal injury. Accordingly, the thermochemical ablation techniques described herein may be used to treat larger tumors in one or two sessions with fewer complications from acid (or base) load toxicity. 
     The thermochemical ablation reagents  115  and  125  that are infused into the targeted tissue  50  may be selected to provide a suitable energy deposition in tissue and to provide other features, such as hyperosmolarity. In some embodiments, the first thermochemical ablation reagent  115  may comprise an acid. For example, the first thermochemical ablation reagent  115  may comprise an acid selected from the group consisting of acetic acid, peracetic acid, hydrochloric acid, hydrobromic acid, hydriodic acid, sulfuric acid, nitric acid, nitrous acid, perchloric acid, phosphoric acid, oxalic acid, pyruvic acid, malonic acid, amino acids (e.g., carboxylic acid derivatives), and the like. Also in some embodiments, the second thermochemical ablation reagent  125  may comprise a base. For example, the second thermochemical ablation reagent  125  may comprise a base selected from the group consisting of KOH, NaOH, NH 4 OH, Ca(OH) 2 , NaHCO 3 , K 2 CO 3 , BuLi, NaOEt or NaSEt (e.g., Na or K salts of alkoxides or thio analogues), NaH, KH, particular amines, and the like. 
     As previously described, the particular acid and the particular base may be selected to product the desired heat generation and low toxicity byproducts. For example, in some embodiments, the first thermochemical ablation reagent  115  may be either acetic acid or hydrochloric acid, and the second thermochemical ablation reagent  125  may be NaOH, NaOEt, or NH 4 OH. Accordingly, the fluid delivery device  130  maintains the first thermochemical ablation reagent  115  separate from the second thermochemical ablation reagent  125  until the reagents  115  and  125  reach the distal portion  134  and are simultaneously infused into the targeted tissue  50  where the reagents  115  and  125  mix and chemically react with one another to generate the ablation heat energy. Moreover, the infusion of the base reagent in addition to the acid reagent can neutralize or other reduced the acid load applied to the patient during the treatment, thereby alleviating some of the problems associated with acid load toxicity. The byproducts from the chemical reaction of the first and second reagents  115  and  125  may further benefit the ablation process, for example, due to the hyperosmolarity of the environment. 
     It should be understood from the description herein that, in other embodiments, the thermochemical ablation reagents  115  and  125  may include other reactive substances. For example, the first thermochemical ablation reagent  115  may comprise electrophiles, and the second ablation reagent  125  may comprise nucleophiles. In some embodiments, the first thermochemical ablation reagent  115  may include an electrophile selected from the group consisting of acetic anhydride, acetyl chloride, acetyl bromide, other anhydrides, other acid halides, and the like. In these circumstances, the second thermochemical ablation reagent  125  may comprise a nucleophile selected from the group consisting of alkoxides, thio analogues, mercaptans (e.g., sulfhydryl), some amines, and the like. Other nucleophiles can include alcohols, sugar molecules, water, and endogenous nucleophiles. Furthermore, in some embodiments, the second thermochemical ablation reagent  125  may comprise a nucleophile selected from the group of previously described bases (e.g., NaOH, NaOEt, NH 4 OH, or the like). Thus, some exemplary embodiments of the fluid delivery device  130  can infuse an electrophile (such as acetyl chloride) with a nucleophile (such as NaOH) that chemically react with one another. The byproducts of the chemical reaction may provide significant heat generation while at least partially neutralizing the acid (or base) load. Such thermochemical ablation techniques described herein may be used to treat larger tumors in relatively few sessions with reduced complications from acid or base load toxicity. 
     It should be understood from the description herein that, in other embodiments, the thermochemical ablation reagents  115  and  125  may include other reactive substances. For example, the first thermochemical ablation reagent  115  may comprise particular oxidizing agents, and the second ablation reagent  125  may comprise certain reducing agents. Finally, in some embodiments, the thermochemical ablation reagents could be chosen to have useful imaging or other analyzable features (e.g., fluorescence, nuclear isotopes, MR imaging characteristics, or the like) to permit a physician to evaluate the reagent distribution in the targeted tissue  50  and throughout the body. 
     In some embodiments, one or both of the thermochemical ablation reagents  115  and  125  may be mixed with a denaturing agent that enhances the tissue ablation process. For example, a denaturing agent such as a sclerosant, detergent, urea, or sodium perchlorite (or another substance from the Hofmeister series) can be added to the first reservoir  110  to mix with the first reagent  115  prior to injection through the delivery device  130 . The denaturing agent may act upon the targeted tissue  50  to enhance the ablation effects caused by the thermochemical reaction of the first reagent  115  and the second reagent  125 . 
     Moreover, in some embodiments, a drug may be added to one or both of the thermochemical ablation reagents  115  and  125  so as to provide a pharmacological effect on the targeted tissue in addition to the thermochemical ablation effects. In one example, a chemotherapy drug can be added to the second reservoir  120  to mix with the second reagent  125  prior to injection through the delivery device  130 . The chemotherapy drug can be administered to the targeted tissue  50  through the delivery device  130  to provide pharmacological effects contemporaneously with the ablation effects from thermochemical reaction of the first reagent  115  and the second reagent  125 . 
     Still referring to  FIG. 1 , some embodiments of the thermochemical ablation system  100  may include a medical imaging system that provides real-time monitoring of the device  130  insertion and the delivery of the reagents  115  and  125 . For example, the medical imaging system can include an ultrasound imaging system  190  to enable a physician or other user to view the distal portion  134  of the fluid delivery device  130  in the targeted tissue  50 . In this embodiment, the ultrasound imaging system  190  includes an ultrasound probe device  192  that can be manipulated on the outside of the patient&#39;s body or within a body cavity. The ultrasound probed  192  may be connected to an ultrasound display system  194  that interprets the signals from the probe  192  and generates a display of the targeted portion of the patient&#39;s body. For example, as shown in  FIG. 1 , the ultrasound display system  194  may show the distal portion  134  of the device  130  as it is inserted into the targeted tissue  50  for delivery of the thermochemical ablation reagents  115  and  125 . It should be understood that, in other embodiments, the imaging system may comprise another type of system other than the ultrasound imaging system  190 . For example, the medical imaging system may include a CT imaging system or the like. Some or all of the delivery device  130  may comprise materials that are compatible with the selected imaging system so as to enable monitoring of the delivery device  130  during insertion. For example, the cannula  140  may comprise a metallic material that can be visualized using the ultrasound imaging system  190 . In another example, the distal portion  134  of the delivery device  130  may include magnetic resonance markers or other features that permit viewability using the selected imaging system. Furthermore, in some embodiments, the delivery device  130  may include depth markers that are directly viewable to the physician or other user. For example, the cannula  140  may include a number of depth markers on the outer surface of the needle body  146 . The physician or other user can view these depth markers during insertion of the cannula  140  through the skin  40  to indicate the approximate depth of insertion. 
     Referring to  FIG. 2 , the distal portion  134  of the fluid delivery device  130  may include one or more side ports  145   a - b  in the cannula  140 . As previously described, the side ports  145   a - b  can be used to radially disperse the first and second thermochemical ablation reagents  115  and  125  and thereby mix the reagents  115  and  125  in the region proximate the distal portion  134 . Such radial dispersion of the thermochemical ablation reagents can improve the mixing of the reagents  115  and  125  upon exiting cannula  140  (e.g., due to increased turbulence). The first and second lumens  142  and  144  maintain the reagents  115  and  125  separate from one another until they reach the distal portion  134  and are dispensed from the ports, after which the reagents are capable of generating an exothermic chemical reaction for ablating the targeted tissue. In such circumstances, the radial dispersion through the side ports  145   a - b  can more evenly distribute the heat generated by the mixing of the reagents  115  and  125 . 
     It should be understood that, in some embodiments, the first and second thermochemical ablation reagents  115  and  125  may be at least partially mixed in the distal portion  134  immediately before being dispensed from the side ports  145   a - b  (refer, for example, to  FIG. 3 ). Also, in other embodiments, the number of first side ports  145   a  and second side ports  145   b  may be different than that depicted in  FIG. 2 . For example, the cannula  140  may include only one first side port  145   a  and only one second side port  145   b . In another example, the cannula  140  may include three, four, five, six, seven, eight, nine, ten, or more of the first side ports  145   a . Also, the cannula  140  may include three, four, five, six, seven, eight, nine, ten, or more of the second side ports  145   b . Furthermore, in some embodiments, the number of first side ports  145   a  may be different from the number of second side ports  145   b . For example, the cannula  140  may include three of the first side ports  145   a  and four, five, or six of the second side ports  145   b.    
     In this embodiment depicted in  FIG. 2 , the first lumen  142  is arranged coaxial with the second lumen  144 . For example, the internal tube  147  may be disposed within the needle body  146  of the cannula  140  so as to define at least a portion of the first lumen  142  within the internal tube  147  and to define at least a portion of the second lumen  144  between the internal tube  147  and the needle body  146 . The internal tube  147  may comprise a generally rigid material, such as stainless steel, a rigid polymer, or the like. Alternatively, the internal tube may comprise a non-metallic material (e.g., biocompatible polymer) that is assembled into the generally rigid needle body  146 . It should be understood that, in other embodiments, the first and second lumens  142  and  144  may be arranged in the cannula  140  in a manner other than coaxial. For example, the first and second lumens  142  and  144  may be arranged in a side-by-side configuration (refer, for example, the embodiment described in connection with to  FIG. 3 ). 
     Still referring to  FIG. 2 , the first lumen  142  is in fluid communication with the first set of side ports  145   a  such that the first thermochemical ablation agent  115  can be delivered through the first lumen  142  and out through the side ports  145   a . Also, the second lumen  144  is in fluid communication with the second set of side ports  145   b  such that the second thermochemical ablation  125  agent can be delivered through the second lumen  144  and out through the side ports  145   b . The walls that at least partially defines the first and second lumens (e.g., in this embodiment, the needle body  146  and the internal tube  147 ) are configured to maintain the reagents  115  and  125  separate from one another until they reach the distal portion  134  and are dispensed from the ports  145   a - b . Upon dispensation from the side ports  145   a - b , the thermochemical ablation reagents  115  and  125  can mix with one another to generate an exothermic chemical reaction—thereby using chemical reaction energy to ablate the targeted tissue. 
     In this embodiment, the cannula  140  includes a closed distal end  143 . As such, the thermochemical ablation reagents  115  and  125  are dispensed from the side ports  145   a - b  rather than from end ports in the distal end  143 . In some embodiments, the distal end may be formed with one or more end ports, and those end ports are plugged or otherwise sealed to ensure that the thermochemical ablation reagents  115  and  125  are dispensed only from the side ports  145   a - b . As previously described, the side ports  145   a - b  can be used to radially disperse the first and second thermochemical ablation reagents  115  and  125 , which can improve the mixing of the reagents  115  and  125  upon exiting cannula  140  (e.g., due to increased turbulence) and can more evenly distribute the heat generated by the mixing of the reagents  115  and  125 . 
     Still referring to  FIG. 2 , some embodiments of the fluid delivery device  130  may include one or more sensors arranged on the distal portion  134 . For example, in this embodiment, the distal portion  134  includes at least one temperature sensor  148  disposed at or near an outer surface of the cannula  140 . The temperature sensor  148  may comprise a thermocouple instrument, such as a type K thermocouple, that has leads incorporated into the body of the cannula  140  (e.g., electrical lines embedded into the walls, insulated electrical traces formed on an inner or outer wall, or the like). The leads may extend from the temperature sensor  148  back to the proximal portion  132  ( FIG. 1 ) of the fluid delivery device  130  so as to connect with a sensor computer system (not shown in  FIGS. 1-2 ). The sensor computer system may be configured to indicate a temperature of the tissue disposed near the temperature sensor  148  based upon signals communicated from the temperature sensor  148 . Such temperature information may be used, for example, by a physician or other user during the procedure to monitor the ablation of the targeted tissue. 
     In another example of a sensor, the distal portion  134  of the delivery device  130  may include at least one pH sensor  149  arranged disposed proximate an outer surface of the cannula  140 . The temperature sensor  149  may comprise a pH probe instrument that has an electrical lead incorporated into the body of the cannula  140  (e.g., electrical lines embedded into the walls, insulated electrical traces formed on an inner or outer wall, or the like). The lead may extend from the pH sensor  149  back to the proximal portion  132  ( FIG. 1 ) of the fluid delivery device  130  so as to connect with a sensor computer system (not shown in  FIGS. 1-2 ). The sensor computer system may be configured to indicate a pH level of the material proximate the distal portion based upon signals communicated from the pH sensor  149 . Such pH information may be used, for example, by a physician or other user during the procedure to monitor the acid load applied to the tissue during the delivery of the thermochemical ablation reagents  115  and  125 . 
     Referring now to  FIG. 3 , some embodiments of the fluid delivery device may include a multi-lumen cannula in which at least one lumen is not arranged in a coaxial configuration. In this embodiment, an alternative distal portion  134 ′ of the fluid delivery device includes a cannula  240  having at least two lumens  242  and  244  in a non-coaxial configuration. The first lumen  242  is arranged adjacent to the second lumen  244 . For example, the first and second lumens  242  and  244  may be at least partially defined by two adjacent bores form through the cannula  140 . In such circumstances, the cannula  140  may comprise a generally rigid needle body  246  in which the first and second lumens  242  and  244  are formed and thereby separated by an intermediate wall portion  247 . 
     Accordingly, the walls that at least partially define the lumens (e.g., in this embodiment, the needle body  246  and the intermediate wall portion  147 ) are configured to maintain the reagents  115  and  125  separate from one another until they reach the distal portion  134 ′. Thereafter, the first and second reagents  115  and  125  can at least partially mix (via internal ports  248   a  and  248   b ) before dispensing from the cannula  240 . The first internal port  248   a  permits a portion of the first reagent  115  from the first lumen  242  to pass into the second lumen  244  in order to mix with a portion of the second reagent  125  in the distal portion  134 ′. Also, the second internal port  248   b  permits a portion of the second reagent  125  from the second lumen  244  to pass into the first lumen  242  in order to mix with a portion of the first reagent  115  in the distal portion  134 ′. In some circumstances, a portion of the first and second reagents  115  and  125  can mix with one another within the distal portion  134 ′, and other portions of the first and second reagents  115  and  125  can mix after being dispensed from the ports of the distal portion  134 ′. By mixing at least a portion of the first and second thermochemical ablation reagents  115  and  125  in the distal portion  134 ′ before dispensation into the targeted tissue, some portion of the dispensed fluid can be heated from the exothermic chemical reaction immediately before dispensation into the targeted tissue. It should be understood that, in other embodiments, the cannula  240  may not include the internal ports  248   a - b  so that the first and second reagents  115  and  125  do not mix within the distal portion  134 ′ (e.g., mix after being dispensed from the distal portion  134 ′). 
     Similar to previously described embodiments, the distal portion  134 ′ may include one or more side ports  245   a - b  in the cannula  240  that can be used to radially disperse the first and second thermochemical ablation reagents  115  and  125 . This radial dispersion of the thermochemical ablation reagents  115  and  125  can be used to mix at least a portion of the reagents  115  and  125  in the region proximate the distal portion  134 ′ and that thereby generate an exothermic chemical reaction for ablating the targeted tissue. Further, the radial dispersion of the fluid from the side ports  245   a - b  can be used to more evenly distribute the heat energy from the exothermic chemical reaction. As shown in  FIG. 3 , a first set of side ports  245   a  extend from the first lumen  242 , a second set of side ports  245   b  extend from the second lumen  244 . The number of first side ports  245   a  and second side ports  245   b  may be different than that depicted in  FIG. 3 . 
     Still referring to  FIG. 3 , in this embodiment, the cannula  240  includes a distal end having end ports  243   a  and  243   b . The first end port  243   a  extends from the first lumen  242  such that the first thermochemical ablation agent  115  (and the portion of the combined first and second reagent  115  and  125  mixed via the internal port  248   b ) can be delivered through the first lumen  242  and out through the first end port  243   a . Also, the second end port  243   b  extends from the second lumen  244  such that the second thermochemical ablation agent  125  (and the portion of the combined first and second reagent  115  and  125  mixed via the internal port  248   a ) can be delivered through the second lumen  244  and out through the second end port  243   b . Thus, the thermochemical ablation reagents  115  and  125  can be dispensed from the end ports  243   a  and  243   b  in addition to side ports  245   a  and  245   b . When the unmixed portion of the first reagent  115  is delivered through the first end port  243   a  and the unmixed portion of the second reagent  125  is delivered from the second end port  243   b , the unmixed portions of reagents  115  and  125  can subsequently mix and react with one another in a region distal of the cannula  240 . In these circumstances, the physician or other user can manipulate the cannula  240  so as to delivery the thermochemical ablation energy to regions radially outward from the distal portion  134 ′ and distally forward of the distal portion  134 ′. It should be understood that, in some embodiments, the cannula  240  having non-coaxial lumens  242  and  244  may include a closed distal end similar to that described in connection with  FIG. 2 . 
     In particular embodiments, the distal portion  134 ′ of the fluid delivery device may include one or more sensors arranged on the cannula  240 . For example, the cannula  240  may incorporate a temperature sensor (e.g., sensor  148  described in connection with  FIG. 2 ), a pH sensor (e.g., sensor  149  described in connection with  FIG. 2 ), or the like. Such sensors may provide useful information to the physician or other user during the ablation procedure. 
     In alternative embodiments, the cannula  240  may include end ports  243   a - 243   b  without any side ports  245   a - b . In such embodiments, one or more end ports  243   a  may extend from the first lumen  242 , and one or more end ports  243   b  may extend from the second lumen  244 . The first and second thermochemical ablation reagents  115  and  125  would be delivered to the end ports  243   a - b  without an opportunity to pass through side ports  245   a - b . Such a configuration may be used, for example, to ablate a specific and localized region of targeted tissue that is disposed generally distal of the tip of the cannula  240 . It should be understood that, in these embodiments, the first and second lumens may be arranged in a coaxial configuration, in a side-by-side configuration, or a different configuration. 
     Referring now to  FIG. 4 , some embodiments of the fluid delivery device may include a cannula with adjustable side projections that dispense the thermochemical ablation reagents  115  and  125 . In this embodiment, an alternative distal portion  134 ″ of the fluid delivery device includes a cannula  340  having at least two lumens  342  and  344  that can be adjusted relative to an outer needle body  346 . For example, the first lumen  342  may be at least partially defined by a first tube  348  that can be actuated from a proximal position to a distal position so that first side projections  345   a  protrude outwardly from the radial surface of the cannula  340 . Similarly, the second lumen  344  may be at least partially defined by a second tube  347  that can be actuated from a proximal position to a distal position so that second side projections  345   b  protrude outwardly from the radial surface of the cannula  340 . The first and second side projections  345   a - b  may include ports therein that dispense the first and second thermochemical ablation reagents  115  and  125  from the projections. Accordingly, the first and second side projections  345   a - b  can be adjusted from a retracted position (e.g., a position generally within a bore of the outer needle body  346 ) to an extended position (e.g., refer to  FIG. 4 ) so as to penetrate into a wider region of the targeted tissue and further distribute the thermochemical ablation energy during delivery of the reagents  115  and  125 . 
     In this embodiment, the outer needle body  346  comprises a generally rigid material (e.g., stainless steel or the like) and the first and second tubes  348  and  347  comprise a shape memory alloy that exhibits superelastic characteristics when inside the patient&#39;s body. For example, the first and second tubes  348  and  347  may comprise nitinol material or the like, which provides superelastic flexibility during the transition from the retracted position (e.g., the side projections  345   a - b  are constrained generally within a bore of the outer needle body  346 ) to the extended position (e.g., refer to  FIG. 4 ). As such, the side projections  345   a - b  may have a curved shape or other configured that permits the ports of the side projections to be pointed toward particular regions. 
     In use, a physician or other user can direct the distal portion  134 ″ to the targeted tissue under guidance from a medical imaging system  190  ( FIG. 1 ). In such circumstances, the side projections  345   a - b  may be in the retracted position to facilitate insertion of the cannula  340  into the patient. When the targeted tissue is reached by the distal portion  134 ″, the physician or other user may operate a trigger device or other actuator (not shown in  FIG. 4 ) that causes the first and second tubes  348  and  347  to shift positions relative to the outer needle body  346 . For example, the trigger device may cause the first and second tubes  348  and  347  to adjust distally, thereby forcing the side projections  345   a - b  to the extended position radially outward of the cannula  340 . As such, the side projections  345   a - b  act as tines that penetrate into a wider region of the targeted tissue. Thereafter, the physician or other user can adjust the coupler  119  ( FIG. 1 ) or other device so that the first and second thermochemical ablation reagents  115  and  125  are dispensed out of the ports in the side projections  345   a - b . Upon release from the ports, the first and second thermochemical ablation reagents  115  and  125  are mixed with one another in a chemical reaction that generates heat to ablate the targeted tissue. 
     It should be understood that, in some embodiments, the cannula  340  may have lumens  342  and  344  that are arranged in a coaxial configuration, in a side-by-side configuration, or in a different configuration. In alternative embodiments, the first and second thermochemical ablation reagents  115  and  125  may be at least partially mixed in the distal portion  134 ″ immediately before being dispensed from the ports of the side projections  345   a - b  (e.g., similar to embodiments described in connection with  FIG. 3 ). Also, in some embodiments, the cannula  340  may have a number of side ports to dispense the first and second reagents directly from the cannula  340  (in addition to the fluid delivery from the side projections  345   a - b ). Further, in some embodiments, the cannula  340  may have a closed distal end similar to that described in connection with  FIG. 2  or end ports similar to those described in connection with  FIG. 3 . In particular embodiments, the distal portion  134 ″ of the fluid delivery device may include one or more sensors arranged on the cannula  340 . For example, the cannula  340  may incorporate a temperature sensor (e.g., sensor  148  described in connection with  FIG. 2 ), a pH sensor (e.g., sensor  149  described in connection with  FIG. 2 ), or the like. Such sensors may provide useful information to the physician or other user during the ablation procedure. 
     Referring now to  FIG. 5 , some embodiments of a thermochemical ablation system  400  may include a fluid delivery device  430  having a cannula  440  that is at least partially flexible. For example, the cannula  440  may comprise a flexible catheter body  446  that is deliverable through a bodily passageway  45 , including a vein, an artery, a urethra, a rectum, a vagina, an esophagus, or the like. Accordingly, a physician or other user can direct a distal portion  434  of the fluid delivery device  430  through the bodily passageway  45  and toward a targeted tissue  50 ′ (e.g., a tumor, a vasculature occlusion such as varicoceles or varicose veins, a ureteral occlusion, or the like) for ablation or other treatment of the targeted tissue  50 ′. 
     Similar to previously described embodiments, the thermochemical ablation system  400  includes a first fluid reservoir  410  and a second fluid reservoir  420  that are in fluid communication with the thermochemical ablation device  430 . The first reservoir  410  includes the first thermochemical ablation reagent  115 , and the second reservoir  420  includes the second thermochemical ablation reagent  125 . Each of the reservoirs  410  and  420  includes an actuator  412  and  422  that can be adjusted to provide a dispensing force to the reagents  115  and  125 . The first actuator  412  and the second actuator  422  can be mechanically coupled to one another with a coupling  419  so that both actuators  412  and  422  can be simultaneous adjusted. 
     Similar to previously described embodiments, the cannula  340  of the fluid delivery device  430  includes a first lumen  442  in fluid communication with the first reservoir  410  and a second lumen  444  in fluid communication with the second reservoir  420 . Also, the distal portion  434  of the delivery device  430  may include a plurality of fluid ports  445   a - b  to disperse the first and second thermochemical ablation reagents  115  and  125  and thereby mix the reagents  115  and  125  in the region proximate the distal portion  434 . 
     Still referring to  FIG. 5 , this embodiment of the fluid delivery device  430  includes the cannula  440  in the form of a flexible catheter device. For example, the cannula  440  may includes a generally flexible catheter body  446  comprised of a biocompatible polymer. The fluid delivery device  430  may include a steering mechanism (e.g., steering wires, shape memory actuators, or the like) so that the distal tip of the cannula  440  can be navigated through the bodily passageway  45 . The cannula  440  may also include an internal tube  447  that is formed inside the catheter body  446 . As such, the first lumen  442  is at least partially defined by the internal tube  447 , and the second lumen  444  is at least partially defined between the catheter body  446  and the internal tube  447 . Thus, in this embodiment, the first and second lumens  442  and  444  are arranged in a coaxial configuration. In other embodiments, the first and second lumens  442  and  444  can be arranged in a side-by-side configuration or in other configurations. 
     The distal portion  434  of the fluid delivery device  430  may include one or more side ports  445   a - b  through which the first and second reagents  115  and  125  are dispensed into the targeted tissue  50 ′. The side ports  445   a - b  may be oriented so that the thermochemical ablation reagents  115  and  125  are radially dispersed from the distal portion  432 . Such radial dispersion of the thermochemical ablation reagents may provide improved mixing of the reagents  115  and  125  upon exiting the fluid delivery device  430  (e.g., due to increased turbulence). Furthermore, the radial dispersion through the side ports  445   a - b  can more evenly distribute the heat generated by the mixing of the reagents  115  and  125 . It should be understood that, in some embodiments, the cannula  440  may have a closed distal end similar to that described in connection with  FIG. 2  or end ports similar to those described in connection with  FIG. 3 . Also, in alternative embodiments, the cannula  440  may include end ports without any side ports  445   a - b . In particular embodiments, the distal portion  434  of the fluid delivery device  430  may include one or more sensors arranged on the cannula  440 . For example, the cannula  440  may incorporate a temperature sensor (e.g., sensor  148  described in connection with  FIG. 2 ), a pH sensor (e.g., sensor  149  described in connection with  FIG. 2 ), or the like. Such sensors may provide useful information to the physician or other user during the ablation procedure. 
     As shown in  FIG. 5 , the first set of side ports  445   a  may be in fluid communication with the first lumen  442  so that the first thermochemical ablation reagent  115  is evacuated from the side ports  445   a  when the coupler  419  (and first actuator  412 ) is adjusted. Likewise, the second set of side ports  445   b  may be in fluid communication with the second lumen  444  so that the second thermochemical ablation reagent  125  is evacuated from the side ports  445   b  when the coupler  419  (and second actuator  412 ) is adjusted. Accordingly, the fluid delivery device  430  provides for simultaneous infusion of the first and second reagents  115  and  125  into the targeted tissue  50 ′, during which the thermochemical ablation reagents  115  and  125  mix with one another to cause an exothermic chemical reaction. The heat generated from this chemical reaction may be sufficient to ablate at least a portion of the targeted tissue  50 ′ surrounding the distal portion  434  of the fluid delivery device  430 . As previously described, the byproducts of the chemical reaction may include greater heat generation with lower acid (or base) load toxicity because the fluid delivery device  430  infuses two reagents that chemically react with one another (rather than direct injection of a single acidic reagent). It should be understood that, in some embodiments, the first and second thermochemical ablation reagents  115  and  125  may be at least partially mixed (via internal ports) in the distal portion  434  immediately before being dispensed from the side ports  445   a - b  (as described, for example, in connection with  FIG. 3 ). 
     Still referring to  FIG. 5 , the fluid delivery device  430  may optionally include an expandable balloon device  441  disposed along the distal portion  434 . The expandable balloon device  441  may be used to anchor the distal tip of the cannula  340  in a desired location with the bodily passage way  45 . Alternatively, the expandable balloon may be used to temporarily seal the bodily passageway  45  during the delivery of the thermochemical ablation reagents  115  and  125  from the catheter body  446 . For example, the balloon  441  may be filled in saline or another fluid to press against the wall of a vein or artery, thereby temporarily hindering blood flow through that portion of the vein or artery. The thermochemical ablation reagents  115  and  125  can be dispensed as previously described while the balloon  441  is expanded, which permits the reagents  115   125  to mix with one another in proximity to the targeted tissue and without being carried away by ordinary blood flow. After the ablation procedure is completed, the balloon may be collapse for removably of the fluid delivery device  430 . 
     Some embodiments of the thermochemical ablation system  400  may include a medical imaging system that provides real-time monitoring of the device  430  insertion and the delivery of the reagents  115  and  125 . For example, the medical imaging system can include an ultrasound imaging system  190  (refer, for example, to  FIG. 1 ) to enable a physician or other user to view the distal portion  434  of the fluid delivery device  430  in the targeted tissue  50 ′. In another example, the medical imaging system may include a CT imaging system or the like. The delivery device  430  may comprise one or more materials that are compatible with the selected imaging system so as to enable monitoring of the delivery device  430  during insertion. For example, the cannula  440  may comprise a metallic material that can be visualized using the ultrasound imaging system  190 . In another example, the catheter body  446  of the cannula  440  may include magnetic resonance markers inserted therein which provide viewability using the selected imaging system. Furthermore, in some embodiments, the delivery device  430  may include depth markers that are directly viewable to the physician or other user. For example, the outer catheter body  446  may include a number of depth markers. The physician or other user can view these depth markers during insertion of the cannula  140  through the skin  40  to indicate the approximate depth of insertion. Accordingly, a physician or other user can direct a distal portion  434  of the fluid delivery device  430  through the bodily passageway  45  and toward a targeted tissue  50 ′ (e.g., a tumor, a vasculature occlusion such as varicoceles or varicose veins, a ureteral occlusion, or the like) for ablation or other treatment of the targeted tissue  50 ′. 
     The thermochemical ablation systems described herein may be employed in minimally invasive techniques to ablate solid tumors or other targeted tissue. These ablation techniques may induce chemical reactions to generate heat for ablation energy. Such chemical reactions may be induced by mixing at least one acid reagent and at least one base reagent, which can neutralize or otherwise reduce the acid load applied to the patient during the procedure. As previously described, other reagents can be used to induce the desired exothermic chemical reaction. The thermochemical ablation techniques described herein can be used to treat solid tumors that arise in number of circumstances, including liver cancer, lung cancer, renal cancer, breast cancer, prostate cancer, sarcomas, or the like. Furthermore, the thermochemical ablation techniques described herein can be used to treat other targeted tissue, such as occlusions that arise in bodily passage ways. Finally, the thermochemical ablation techniques described herein are not limited to use in human patients. For example, the thermochemical ablation systems described herein may be used to treat other animal patients, including mammalian patients. 
     A number of embodiments of the invention have been described. Nevertheless, it will be understood that various modifications may be made without departing from the spirit and scope of the invention. Accordingly, other embodiments are within the scope of the following claims.