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Questions and Answers
What occurs to the heating time required to produce cell killing above the break point temperature of 43°C?
What occurs to the heating time required to produce cell killing above the break point temperature of 43°C?
Which of the following statements is true regarding the mechanisms of cell killing by heat?
Which of the following statements is true regarding the mechanisms of cell killing by heat?
How does the surviving fraction of cells change below 43°C during heating?
How does the surviving fraction of cells change below 43°C during heating?
What is the formula to calculate the surviving fraction of cells in the active sample?
What is the formula to calculate the surviving fraction of cells in the active sample?
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What differentiates heat-induced cell killing mechanisms from ionizing radiation?
What differentiates heat-induced cell killing mechanisms from ionizing radiation?
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What temperature rise is characteristic of thermal ablation in cancer treatment?
What temperature rise is characteristic of thermal ablation in cancer treatment?
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Which of the following methods utilizes mechanical waves to induce heating in tissues?
Which of the following methods utilizes mechanical waves to induce heating in tissues?
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What is the general cellular response to temperatures exceeding 43°C?
What is the general cellular response to temperatures exceeding 43°C?
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Which method of immunotherapy is most associated with using a high-intensity ultrasound to induce thermal effects?
Which method of immunotherapy is most associated with using a high-intensity ultrasound to induce thermal effects?
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What factor primarily affects the survivability of cells exposed to heat below 43°C?
What factor primarily affects the survivability of cells exposed to heat below 43°C?
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Which of the following correctly describes the mechanism of action for shortwave diathermy?
Which of the following correctly describes the mechanism of action for shortwave diathermy?
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What kind of temperature exposure time is associated with conventional hyperthermia treatment?
What kind of temperature exposure time is associated with conventional hyperthermia treatment?
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Which electromagnetic method causes dipole rotation in tissues leading to heating?
Which electromagnetic method causes dipole rotation in tissues leading to heating?
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What happens to blood flow in tumors after exposure to heat above 42.5°C?
What happens to blood flow in tumors after exposure to heat above 42.5°C?
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What is the effect of mild hyperthermia on tumor oxygenation?
What is the effect of mild hyperthermia on tumor oxygenation?
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What factor mainly complicates achieving uniform heat distribution in tumor tissue during hyperthermia?
What factor mainly complicates achieving uniform heat distribution in tumor tissue during hyperthermia?
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How does hyperthermia cytotoxicity relate to temperature and exposure time?
How does hyperthermia cytotoxicity relate to temperature and exposure time?
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What is the role of the thermal dose concept in hyperthermia treatments?
What is the role of the thermal dose concept in hyperthermia treatments?
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What is the breakpoint temperature regarding hyperthermia treatment efficacy?
What is the breakpoint temperature regarding hyperthermia treatment efficacy?
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According to thermal dose calculations, how does temperature above 43°C affect exposure time for cytotoxicity?
According to thermal dose calculations, how does temperature above 43°C affect exposure time for cytotoxicity?
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How do tumor and normal tissues respond differently to heat increase during hyperthermia?
How do tumor and normal tissues respond differently to heat increase during hyperthermia?
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What is the defined value of R in thermal dose calculations for temperatures above 43°C?
What is the defined value of R in thermal dose calculations for temperatures above 43°C?
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Which is a potential outcome of utilizing mild hyperthermia in cancer treatment?
Which is a potential outcome of utilizing mild hyperthermia in cancer treatment?
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Which cell type is most likely to show an increase in heat sensitivity due to environmental conditions?
Which cell type is most likely to show an increase in heat sensitivity due to environmental conditions?
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What is the main challenge associated with heat therapy for tumors?
What is the main challenge associated with heat therapy for tumors?
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What effect does prior heat treatment have on cells when exposed to heat again, a phenomenon known as thermotolerance?
What effect does prior heat treatment have on cells when exposed to heat again, a phenomenon known as thermotolerance?
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Which of the following best describes heat shock proteins (HSPs)?
Which of the following best describes heat shock proteins (HSPs)?
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Which aspect of tumor vasculature affects heat delivery during hyperthermia treatment?
Which aspect of tumor vasculature affects heat delivery during hyperthermia treatment?
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What is the primary reason heat therapy is often performed in one or two sessions as opposed to fractionated treatments?
What is the primary reason heat therapy is often performed in one or two sessions as opposed to fractionated treatments?
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In terms of cell types, which condition is true regarding their sensitivity to heat?
In terms of cell types, which condition is true regarding their sensitivity to heat?
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Which of the following is NOT a factor affecting the survival fraction of cells in heat treatment?
Which of the following is NOT a factor affecting the survival fraction of cells in heat treatment?
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What role do Heat Shock Proteins play in the cellular response to heat?
What role do Heat Shock Proteins play in the cellular response to heat?
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Which statement about the breakpoint temperature in cancer therapy is correct?
Which statement about the breakpoint temperature in cancer therapy is correct?
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Study Notes
Hyperthermia and Thermal Ablation for Cancer Treatment
- Hyperthermia is a treatment that raises tissue temperature to damage or kill cancer cells or enhance their sensitivity to other treatments (e.g., radiotherapy, chemotherapy).
- Historically, heat has been a common medical therapy for various diseases, including cancer.
- Hippocrates, considered the "Father of Medicine" (470-377 BC), noted the potential of heat for healing.
- Shortwave diathermy, radiofrequency (RF) capacitive heating, microwaves, ultrasound, and lasers are methods of locally heating tissue for cancer treatment.
- Conventional hyperthermia involves a mild temperature rise over extended periods (minutes to hours).
- Thermal ablation involves a higher temperature rise over shorter periods (less than a few minutes), a good example of which is high-intensity focused ultrasound (HIFU).
Cellular Response to Heat
- Mammalian cells are highly sensitive to heat.
- Heat kills cells in a predictable and repeatable manner.
- Studies on heat's effect on cells often use controlled water-bath heating systems.
- Cell survival curves differ for temperatures below and above 43°C.
- For temperatures above 43°C, the curves resemble those associated with ionizing radiation.
- For temperatures below 43°C, cell survival curve analysis is more complex.
Surviving Fraction Calculation
- In vitro cell culture is a standard method for studying responses to heat and radiation.
- In vitro survival curves aid in understanding radiation biology.
- Calculating the surviving fraction involves the following: Surviving Fraction = (Number of colonies counted in the active sample) / (Number of cells seeded in the active sample) x (Plating Efficiency / 100)
- Typically, two samples are used in the study, a control (sham) sample, and an active sample exposed to heat or radiation to assess effects.
Temperature Break Point for Mammalian Cells
- Different cells exhibit varied heat sensitivities.
- 43°C marks a crucial point for most mammalian cells, impacting their cytotoxic response and thermotolerance.
- Below 43°C, thermotolerance develops gradually during the heating process.
- Above 43°C, the time needed to reach a certain level of cell killing is halved with each 1°C increase in temperature.
- This difference indicates distinct intracellular mechanisms govern cell killing above and below this threshold point.
Mechanisms of Cell Killing by Heat
- Heat-induced cell killing mechanisms differ significantly from those of ionizing radiation.
- Proteins, particularly nuclear proteins, are the primary heat-sensitive targets for cytotoxicity.
- Heat causes protein denaturation, affecting structural components like chromosomes, nuclear matrix, cytoskeleton, repair enzymes, and membrane proteins.
- Mechanisms involved in heat cytotoxicity differ above and below the temperature break point (43°C).
Heat Sensitivity and Cell Age
- Heat-induced cell survival complements ionizing radiation's cell survival functions.
- The late S phase of the cell cycle shows higher sensitivity to heat than other phases.
- Combining radiotherapy and hyperthermia can enhance cancer cell killing efficiency (synergistic effect).
Effects of pH and Nutrients on Sensitivity to Heat
- Cells in acidic (low pH) environments are more susceptible to heat-induced killing.
- Cells deficient in nutrients display increased heat sensitivity.
- Hypoxic cells exhibit a similar sensitivity to heat as oxic cells and may show increased heat sensitivity.
- Cancer cells in tumors often have low pH, low nutrient levels, and reduced oxygen levels (hypoxic) making them more susceptible to heat.
Thermotolerance
- Thermotolerance is the development of transient resistance to subsequent heating after an initial heat treatment.
- Thermotolerance results in systematic reduction of the slope of subsequent heat treatments' cell survival curves.
- Fractionated hyperthermia treatments, unlike radiotherapy, are typically administered in a limited, single session therapy
Thermal Dose
- The threshold for irreversible thermal damage in tissues depends on the tissue type.
- For most soft tissues, experimental thresholds for irreversible damage (coagulative necrosis) are >120 minutes at 43°C and >240 minutes at 43°C are widely accepted.
- More sensitive tissues (e.g., nerves) show lower thresholds for irreversible damage.
Thermal Dose Calculation—Example
- Calculating the total thermal dose requires integration of the time-varying temperature over the heating period.
- This evaluation considers a given temperature's effectiveness (R values) above and below a critical temperature (43°C) in calculating the heat dose.
Tissue Temperature Variation in Hyperthermia
- In hyperthermia application, the system delivers a burst of heat, causing the temperature inside treated tissue to quickly increase until a target temperature is reached, and then decreasing slowly back to normal body temperature after the treatment.
Bio-Heat Transfer Equation (BHTE)
- Bio-Heat Transfer Equation (BHTE) is a mathematical model used to predict temperature changes in the body tissues during heat treatments.
- BHTE considers numerous factors affecting heat transfer in tissue, such as tissue/blood temperature in °C, perfusion rate, blood vessel heat tolerance etc..
Heat Production Rate (Q) in Ultrasound Hyperthermia
- This formula models the heat produced in tissue during ultrasound-based hyperthermia treatment.
- The equation demonstrates how the heat production rate (Q) in tissue depends on the intensity and absorption coefficient of the ultrasound waves.
Interaction Between Heat and Radiation
- The combined use of heat and ionizing radiation leads to a synergistic cytotoxic effect, resulting in a greater cell killing effect than applying either modality individually.
- Hyperthermia typically does not impact the extent of DNA damage caused by radiation.
- Synergy from combining thermal and radiation therapies are driven by three factors: the sensitivity of specific cell cycle stages to thermal and radiation treatments, the influence of cellular environmental conditions (nutrient levels and pH), and the impact on DNA damage repair mechanisms.
Thermal Enhancement Ratio (TER)
- The thermal enhancement ratio (TER) quantifies the combined effect of radiation and heat on cell killing.
- It is the ratio of radiation doses needed to achieve a specified level of damage with and without hyperthermia treatment.
- The magnitude of the TER depends on the specific cell type, radiation type, and the extent of the heat application.
Heat and Chemotherapy
- Hyperthermia can enhance the cytotoxicity of some chemotherapeutic agents, but this effect is not universal.
- Increased cell killing with chemotherapeutic agents in high-temperature environments is directly mediated through higher concentration of heat shock proteins in the treated cells.
Thermal Ablation of Tumors using Ultrasound—High Intensity Focused Ultrasound (HIFU)
- HIFU is a thermal ablation technique using focused ultrasound.
Ultrasound—An Interdisciplinary Topic
- Ultrasound has extensive applications in various fields, including medicine and industrial applications.
- Various disciplines, such as physics, electrical engineering, mechanical engineering, materials engineering, and computer engineering, combine to create and utilize ultrasound technologies.
Ultrasound is a Wave Phenomenon
- Sound waves are disturbances or fluctuations traveling through a medium.
Ultrasound Imaging
- Ultrasound frequency has a crucial impact on imaging capabilities and modalities.
- Various ultrasound frequencies are used for imaging different parts of the human body.
Therapeutic Ultrasound
- Therapeutic ultrasound applications encompass both high-and low-intensity treatments.
- High-intensity applications involve tissue heating, coagulation of soft tissue, mechanical destruction of soft tissue, and lithotripsy
Image-Guided HIFU Surgery
- Image-guided HIFU treatment has applications in oncology, cosmetic surgery, and neurosurgery.
HIFU – A Non-Invasive Surgery Modality
- HIFU involves high-intensity focused ultrasound bursts. These targeted energy bursts are far more intense than regular ultrasound used in diagnostics.
HIFU—Main Features
- HIFU utilizes high ultrasound intensities, focused beam, and specific frequency ranges
- HIFU has rapid temperature rises at the focus and is used in targeted areas for precise, noninvasive procedures
- HIFU is a thermal ablation technique used for various medical applications.
Mechanisms of Action with Tissue
- HIFU's mechanism involves both direct (thermal coagulation & non-thermal effects (mechanical stress, cavitation), indirect (enhancing immune system effects and anti-tumor responses) mechanisms within the body.
Regions of Facial Treatment
- Regions of the face targeted by Image-guided HIFU treatments include eyebrow lifts, periorbital wrinkles, nasolabial folds, and skin tightening.
Clinical Advantages
- Image-guided HIFU offers several clinical advantages, including reduced treatment time, elimination of anesthetic needs, avoidance of skin cooling procedures, and minimised downtime post-procedure
Example—Forehead Treatment
- A diagram shows how HIFU treatment works on the forehead, targeting different layers of skin tissue for wrinkle reduction
Results—Eyebrow Lift in Ninety Days
- Images displayed demonstrate the results of HIFU-based eyebrow lift procedures over ninety days.
Results—Forehead Wrinkles
- Images show before and after results of HIFU forehead treatment targeting wrinkles.
HIFU in Cosmetic Surgery—Conclusions
- HIFU has demonstrated safety and efficacy, and FDA clearance was obtained in 2009 for these applications.
Design and Development of a Medical Device (Product Development Cycle)
- The development of a new medical device like those used for HIFU involves a multidisciplinary approach combining various areas of expertise (engineering, business, biology, and medicine)
- Specific stages include initial requirements, R&D (design and testing), clinical testing/regulatory clearances, marketing, production, and after-sales service support.
A Novel Technique to Treat Prostate Cancer
- HIFU shows significant potential for prostate cancer treatment. This minimally invasive approach has been used in thousands of cancer patients.
HIFU Prostate Cancer Treatment
- HIFU is used in transrectal procedures involving the prostate.
Image-guided HIFU in Cosmetic Surgery
- Image-guided HIFU is applied in cosmetic surgery procedures
- HIFU has become increasingly popular in cosmetic applications, such as wrinkle reduction and eyebrow lifts.
HIFU in Cosmetic Surgery and Dermatology
- HIFU technology is used for both superficial and deeper tissue treatments within the face, targeting multiple layers of skin, including the SMAS, subcutaneous tissue, dermis, and epidermis.
The UltraSite GTTM System—Extracorporeal Approach
- This procedure involves utilizing specialized equipment (the UltraSite GTTM system) to apply HIFU to the exterior of the body, rather than targeting treatment directly within the treated zone.
Regions of Facial Treatment
- Image demonstrates various areas of the face frequently treated with HIFU, targeting brow lifts, wrinkles, and tightening of the skin.
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Description
Explore the fascinating world of hyperthermia and thermal ablation as innovative cancer treatment methods. Learn how these techniques use heat to damage cancer cells or enhance the effectiveness of other treatments. Discover the historical significance and modern applications of these therapies in medical settings.